DE102009034526A1 - 17-Hydroxy-17-pentafluoroethyl-estra-4,9 (10) -diene-11-ethynylphenyl derivatives, process for their preparation and their use for the treatment of diseases - Google Patents

Abstract

The invention relates to 17-hydroxy-17-pentafluoroethyl-estra-4,9 (10) -diene-11-ethynylphenyl derivatives of the formula I, in which Rund X have the meaning given in the claims and the description, $ F1 and a process for their manufacture and their use as medicinal products.

Description

The Invention relates to the subject matter described in the claims, d. H. new 17-hydroxy-13-methyl-17-pentafluoroethyl-11-ethynylphenyl dodecahydro-cyclopenta [a] phenanthren-3-one derivatives with progesterone antagonizing action, process for their preparation, their use for the treatment and / or prophylaxis of diseases and their use for the preparation of medicaments for treatment and / or prophylaxis of diseases.

Compounds with antagonistic action on the progesterone receptor (competitive progesterone receptor antagonists) first became known in 1982 ( RU 486 ; EP 057115 ) and since then intensively studied and described.

Progesterone receptor antagonists with fluorinated 17α-side chain have been reported by U. Fuhrmann et al., J. Med. Chem. 43, 5010-5016 (2000) described and are in the WO 98/134947 claimed. The compounds described there with fluorinated 17α-side chain generally have a very strong antagonistic activity on the progesterone receptor. Very potent and therefore in WO 98/34947 preferred compounds are 11β- (4-acetylphenyl) -20,20,21,21,21-pentafluoro-17-hydroxy-19-nor-17α-pregna-4,9-dien-3-one, 11β- (4- Acetylphenyl) -20,20,21,21,21-pentafluoro-17-hydroxy-19-nor-17α-pregna-4-en-3-one and 6'-acetyl-9,11β-dihydro-17β-hydroxy 17α- (1,1,2,2,2-pentafluoroethyl) -4'H-naphth [3 ', 2', 1 ': 10,9,11] ester-4-en-3-one. These compounds are converted in vivo to a considerable extent in various metabolites, some of which have strong, sometimes lower pharmacological activity. The metabolism predominantly occurs at the 4-substituent of the 11β-phenyl radical.

In WO 2008/058767 compounds are described which are at least in part metabolites of WO 98/34947 are described compounds.

task It is the object of the present invention to provide highly potent competitive progesterone receptor antagonists to provide and thus alternative treatment options gynecological diseases.

It it was found that the compounds of the invention are particularly suitable to solve this problem.

worin
R¹ über eine C-C-Dreifachbindung in Position m oder p am Phenylring angeknüpft ist und für einen Rest -(CH=CH)_n-R², -(CH₂)_q-R³ oder -CH=NOR⁴ steht,
R² Wasserstoff oder eine Aryl-, C₁-C₁₀-Alkyl-, -CO₂R⁶ oder -CN Gruppe ist,
R³ Wasserstoff, NH₂, N₃ oder eine -NHCONHR⁴, -OCONHR⁴, -OR⁵ Gruppe ist,
R⁴ ausgewählt ist aus der Gruppe, umfassend Wasserstoff, C₁-C₁₀-Alkyl, C₂-C₁₀-Alkenyl, Aryl, C₇-C₂₀-Aralkyl, (CH₂)_s-R⁶, CH₂-CO-OR⁶,

worin
R⁵ ausgewählt ist aus der Gruppe, umfassend Wasserstoff, C₇-C₂₀-Aralkyl, CH₂CO₂R⁶, CH₂CN, CH₂CH₂OH,

n für 0 bis 2,
q für 1 oder 2,
s für 1 oder 2,
R⁶ für Wasserstoff, C₁-C₁₀-Alkyl, Aryl, C₇-C₂₀-Aralkyl,
X für Sauerstoff, NOR⁶ oder eine NNHSO₂R⁶ Gruppe, mit R⁶ in der angegebenen Bedeutung, steht.The present invention relates to 17-hydroxy-17-pentafluoroethyl-estra-4,9 (10) -diene-11-methyleneoxyalkylene aryl derivatives having the general chemical formula I:

wherein
R ^{1 is} linked via a C-C triple bond in position m or p to the phenyl ring and a radical is - (CH =CH) _n -R ² , - (CH ₂ ) _q -R ³ or -CH = NOR ⁴ ,
R ^{2 is} hydrogen or an aryl, C ₁ -C ₁₀ alkyl, -CO ₂ R ⁶ or -CN group,
R ^{3 is} hydrogen, NH ₂ , N ₃ or an -NHCONHR ⁴ , -OCONHR ⁴ , -OR ⁵ group,
R ^{4 is} selected from the group comprising hydrogen, C ₁ -C ₁₀ alkyl, C ₂ -C ₁₀ alkenyl, aryl, C ₇ -C ₂₀ aralkyl, (CH ₂ ) _s -R ⁶ , CH ₂ -CO -OR ⁶ ,

wherein
R ^{5 is} selected from the group comprising hydrogen, C ₇ -C ₂₀ aralkyl, CH ₂ CO ₂ R ⁶ , CH ₂ CN, CH ₂ CH ₂ OH,

n for 0 to 2,
q for 1 or 2,
s for 1 or 2,
R ^{6 is} hydrogen, C ₁ -C ₁₀ -alkyl, aryl, C ₇ -C ₂₀ -aralkyl,
X is oxygen, NOR ⁶ or an NNHSO ₂ R ⁶ group, with R ⁶ in the meaning indicated.

Gruppe, kennzeichnet die Stelle an der die Bindung des jeweiligen Restes an die benachbarte Gruppe erfolgt.The arrow, for example, in the

Group, marks the place where the binding of the respective remainder to the neighboring group takes place.

Unless otherwise specified, in the context of the present invention, the substituents have the following meaning:
Alkyl in R ² , R ⁴ and R ⁶ and in other cases are straight-chain or branched-chain alkyl groups with the specified number of carbon atoms or optionally 1-10 carbon atoms, for example methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, nonyl or decyl. The alkyl groups R ² , R ⁴ and R ⁶ may also be perhalogenated, preferably perfluorinated or by 1-5 halogen atoms, hydroxy groups, C ₁ -C ₄ alkoxy groups, C ₆ -C ₁₂ aryl groups (which in turn may be substituted by 1-3 halogen atoms can be substituted). In particular, alkyl may therefore also be hydroxymethylene (HO-CH ₂ ), hydroxyethylene (HO-C ₂ H ₄ ), hydroxypropylene (HO-C ₃ H ₆ ) and hydroxybutylene (HO-C ₄ H ₈ ) and their isomers.

Alkenyl in R ⁴ are straight or branched chain alkenyl groups having 2-10 carbon atoms, such as vinyl, propenyl, butenyl, pentenyl, isobutenyl or isopentenyl.

The alkenyl group R ⁴ may be substituted by 1-5 halogen atoms, hydroxy groups, C ₁ -C ₃ alkoxy groups or C ₆ -C ₁₂ aryl groups (which in turn may be substituted by 1-3 halogen atoms).

Aryl in R ² , R ⁴ and R ⁶ and in other cases are to be understood as meaning aromatic, mono- or bicyclic radicals having generally from 5 to 10 and up to 5 heteroatoms from the series S, O and N, for example Phenyl, naphthyl, furyl, thienyl, pyridyl, pyrazolyl, pyrimidinyl, oxazolyl, isoxazolyl, pyridazinyl, pyrazinyl, quinolyl, thiazolyl or tetrazolyl, which are mono- or polysubstituted by halogen, OH, SO ₂ -alkyl, SO-alkyl and S-alkyl, O-alkyl, CO ₂ H, CO ₂ -alkyl, NH ₂ , NO ₂ , N ₃ , CN, C ₁ -C ₁₀ -alkyl, C ₁ -C ₁₀ -acyl or C ₁ -C ₁₀ -acyloxy groups, may be substituted. As far as otherwise aryl is mentioned as a substituent on alkyl, alkenyl or alkynyl, it is in particular aryl groups having 5-12 ring atoms.

Aralkyl in R ⁴ , R ⁵ and R ⁶ is to be understood as meaning aralkyl groups. Aralkyl represents aralkyl groups which may contain up to 14 carbon atoms, preferably 6-10 carbon atoms in the ring, and 1-8, preferably 1-4, carbon atoms in the alkyl chain. Suitable aralkyl radicals are, for example, benzyl, phenylethyl, naphthylmethyl, naphthylethyl, furylmethyl, thienylethyl or pyridylpropyl. The rings may be mono- or polysubstituted by halogen, OH, O-alkyl, CO ₂ H, CO ₂ -alkyl, NH ₂ , NH (C ₁ -C ₁₀ -alkyl), N (C ₁ -C ₁₀ -alkyl) ₂ , NO ₂ , N ₃ , CN, C ₁ -C ₂₀ alkyl, C ₁ -C ₁₀ perfluoroalkyl, C ₁ -C ₂₀ acyl or C ₁ -C ₂₀ acyloxy groups.

When Heteroatoms come sulfur, oxygen or nitrogen in question, where nitrogen is preferred. As an example, the pyridylpropyl radical called.

So far Alkoxy (O-alkyl) is mentioned, it is alkoxy groups with 1-4 carbon atoms. Alkoxy may in particular methoxy, ethoxy and be propoxy.

As far as acyl (CO-alkyl) is mentioned, it is acyl groups having 1-20 carbon atoms. Acyl may in particular be formyl, acetyl, propionyl and butyryl.

So far Acyloxy (O-CO-alkyl) is mentioned, it is Acyloxygruppen with 1-20 carbon atoms. Acyloxy may in particular formyloxy, Acetyloxy, propionyloxy and butyryloxy.

halogen is fluorine, chlorine or bromine. Among these are fluorine or chlorine prefers.

According to the invention preferred are derivatives in which the group X is an oxygen atom.

in para-Position an den Phenylring geknüpft ist.Preference is furthermore given to compounds in which the group

in the para-position to the phenyl ring is attached.

The Compounds according to the invention of the general Formula I may vary depending on its structure exist in stereoisomeric forms (enantiomers, diastereomers). The invention therefore includes the enantiomers or diastereomers and their respective mixtures including the racemates. From such mixtures of enantiomers and / or diastereomers can the stereoisomerically uniform constituents in known Isolate way.

Everyone said substituent on the steroid backbone can in both an α and a β position available. In addition, the substituents can also on the steroid backbone, which contain a double bond and in which the double bond on each atom has at least one substituent, which is not hydrogen carries both E- and Z-configured available.

Provided the compounds of the invention in tautomers Forms may include the present invention all tautomeric forms.

Furthermore For example, the present invention also encompasses prodrugs of the invention Links. The term "prodrugs" includes compounds, which during their residence in the body too compounds of the invention, for example be implemented by enzymatic or hydrolytic processes.

The Compounds according to the invention of the general Formula I can also be present as solvates, hydrates and salts, whereby also different crystal modifications, as well as α-, β- or γ-cyclodextrin clathrates or liposome-encapsulated Compounds of formula I are included.

When Solvates are in the context of the invention, such forms of the invention Compounds referred to in solid or liquid Condition an adduct formation with solvent molecules demonstrate. If the derivatives of the formula I are present as solvate, the contained solvent in a stoichiometric or too present non-stoichiometric ratio. For stoichiometric solvates, this is also called hemi, (Semi-), mono-, sesqui-, di-, tri-, tetra-, penta-, etc. solvates.

hydrates are a special form of solvates involving coordination done with water.

According to the invention preferred among the solvates are those with water. These are also called Hydrates.

When Salts are physiologically acceptable in the context of the present invention Salts of the compounds according to the invention are preferred. Also included are salts that are suitable for pharmaceutical applications themselves are not suitable but for example for the Isolation or purification of the compounds of the invention can be used.

physiological acceptable salts of the compounds of the invention include - if a basic function is included - salts with inorganic or organic acids, in particular of mineral acids, carboxylic acids and sulfonic acids, z. Salts of hydrochloric acid, hydrobromic acid, sulfuric acid, Phosphoric acid, methanesulfonic acid, ethanesulfonic acid, Toluenesulfonic acid, benzenesulfonic acid, naphthalenedisulfonic acid, Acetic acid, trifluoroacetic acid, propionic acid, Lactic acid, tartaric acid, malic acid, citric acid, Fumaric acid, maleic acid or benzoic acid.

Physiologically acceptable salts of the compounds according to the invention comprise - if one containing acidic function - alkali metal salts, alkaline earth metal salts or ammonium salts, as can be obtained by reaction with corresponding inorganic or organic bases. By way of example and by way of preference, mention may be made of alkali metal salts (for example sodium and potassium salts), alkaline earth metal salts (for example calcium and magnesium salts) and ammonium salts derived from ammonia or organic amines having 1 to 16 carbon atoms, by way of example and preferably ethylamine , Diethylamine, triethylamine, ethyldiisopropylamine, monoethanolamine, diethanolamine, triethanolamine, dicyclohexylamine, dimethylaminoethanol, procaine, dibenzylamine, N-methylmorpholine, arginine, lysine, ethylenediamine, N-methylpiperidine, N-methyl-glucamine, D-methyl-glucamine, ethyl glucamine, 1,6-hexadiamine, glucosamine, N-methylglycine, 2-amino-1,3-propanediol, tris-hydroxy-methyl-aminomethane or 1-amino-2,3,4-butanetriol.

It it was found that the compounds of the invention of the formula (I) surprisingly good, the progesterone have antagonizing effect, without the disadvantages of the compounds of the prior art.

So show most of the compounds of the invention, a surprisingly high metabolic stability in vitro in liver microsomes of rat and human. At the in vivo in the rat tested compounds became partly a low Clearance and a surprisingly long half life in vivo found in the rat. At the same time succeeded, the water solubility significantly improve for some compounds (see example 61).

These Compounds are valuable pharmaceutical agents. You can among other things for the production of pharmaceutical preparations for the treatment of uterine fibroids or endometriosis, severe menstrual bleeding, Meningiomen, hormone-dependent breast carcinomas and with menopausal symptoms or fertility control and emergency contraception.

to Treatment of uterine fibroids or endometriosis can the erfindungemäßen connections simultaneously or sequentially with gestagens or combinations of estrogens and progestins are combined.

In WO 96/15794 (Spicer et al., Balance Pharm. Inc.), WO 96/03130 (Stöckemann et al., Schering AG) and PCT / EP 2009/003249 (Moller et al., Bayer Schering Pharma AG) are disclosed progesterone receptor antagonist / progestin regime. Well suited for the treatment of uterine fibroids and endometriosis are - optionally repeating - regimens in which the progesterone receptor antagonist is given over a period of two to four months, followed by the administration of the progestogen over a period of one to four weeks. Particularly suitable is the - possibly repeated - 84-day administration of the progesterone receptor antagonist followed by the 14-day administration of the gestagen.

to Treatment of tumor diseases can, for. For example, the following Active ingredients / drug classes either simultaneously or sequentially SERMs, SERDs, anti-estrogens, aromatase inhibitors, Kinase inhibitors, angiogenesis inhibitors and / or cytostatics.

to Treatment of complaints associated with menopause comes a simultaneous or sequential administration of erfindungsemäßen Connections z. B. with SERMs, SERDs and estrogens into consideration.

SERMs (Selective Estrogen Receptor Modulators) are those according to the invention Compounds that are tissue-selective either an antiestrogenic or have estrogenic effect, for example, on the uterus, the effect of estrogen inhibit, but on the bone a neutral or estrogen-like Have effect. Examples are clomifene, raloxifene, tamoxifen, torimifen, Bazedoxifene, lasofoxifene and ormeloxifen.

selective Estrogen Receptor Stabilizers (SERDs) are drugs containing the Completely antagonize estrogen receptor and become one Lead to degradation of the receptor.

antiestrogens Compounds that complete the estrogen receptor antagonize, for example, fulvestrant.

aromatase inhibitors inhibit the enzyme aromatase and thus the aromatization of Androgens in estrogens. These include u. a. Anastrozole, Letrozole, Exemestane, Vorozole, Formestane and Fadrozole.

Kinase inhibitors inhibit enzymes that release a phosphate residue from ATP onto other substrates, including the particular to hydroxy groups, transferred, for. Sorafenib (Nexavar) or Imatinib (Gleevec).

Angiogenesis inhibitors, z. B. Avastin, reduce or block the neovascularization and thus the circulation of a tumor.

cytostatics, z. Cis-platin, taxol, taxotere, sagopilone, ixabepilone are natural or synthetic substances that drive tumor cells into apoptosis.

When For the purposes of the present invention, progestins are either natural Progesterone itself understood or synthetic derivatives that like the progesterone itself bind to the progesterone receptor and in Dosages above the ovulation inhibition dose, the Inhibit ovulation. As examples of the synthetic derivatives are the drospirenone, gestodene, levonorgestrel, cyproterone acetate, Desogestrel and 3-ketodesogestrel, norethisterone, norethisterone acetate and called the dienogest.

at Combinations of progestogens and estrogens are involved to the drug combinations that are known in the oral contraceptives, for example Yasmin, Femovan, Triquilar, Marvelon, YAZ etc., are included. The effectiveness of the invention Compounds as a progesterone receptor antagonist have been used in vitro in Transactivation tests and rat in vivo (termination of the early pregnancy).

• – (8S,11R,13S,14S,17S)-17-Hydroxy-11-[4-(3-hydroxy-prop-1-in-1-yl)-phenyl]-13-methyl-17-pentafluorethyl-1,2,6,7,8,11,12,13,14,15,16,17-dodecahydro-cyclopenta[a]phenanthren-3-on (Beispiel 1)
• – [4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-propinsäure (Beispiel 2)
• – [4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-propinsäure-methylester (Beispiel 3)
• – (E)-5-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-pent-2-en-4-innitril (Beispiel 4)
• – (Z)-5-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-pent-2-en-4-innitril (Beispiel 5)
• – (E)-5-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-pent-2-en-4-in-säureethylester (Beispiel 6)
• – 7-(2E/Z,4E/Z)-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-hepta-2,4-dien-6-inylsäureethylester (Beispiel 7)
• – {3-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyloxy}-essigsäuretert-butylester (Beispiel 8)
• – {3-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyloxy}-essigsäuremethylester (Beispiel 9)
• – {3-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyloxy}-essigsäure (Beispiel 10)
• – (8S,11R,13S,14S,17S)-17-Hydroxy-11-{4-[3-(2-hydroxy-ethoxy)-prop-1-in-1-yl]-phenyl}-13-methyl-17-pentafluorethyl-1,2,6,7,8,11,12,13,14,15,16,17-dodecahydro-cyclopenta[a]phenanthren-3-on (Beispiel 11)
• – 3-{(E/Z)-4-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-but-1-en-3-inyl}-benzoesäuremethylester (Beispiel 12)
• – 3-{(E)-4-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-but-1-en-3-inyl}-benzoesäure (Beispiel 13A)
• – 3-{(Z)-4-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-but-1-en-3-inyl}-benzoesäure (Beispiel 13B)
• – {3-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyloxy}-acetonitril (Beispiel 14)
• – 4-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenylethinyl]-benzoesäuremethylester (Beispiel 15)
• – 4-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenylethinyl]-benzoesäure (Beispiel 16)
• – 3-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenylethinyl]-benzoesäuremethylester (Beispiel 17)
• – (8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-17-pentafluorethyl-11-{4-[3-(1H-tetrazol-5-ylmethoxy)-prop-1-in-1-yl]-phenyl}-1,2,6,7,8,11,12,13,14,15,16,17-dodecahydro-cyclopenta[a]phenanthren-3-on (Beispiel 18)
• – 4-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methy)-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenylethinyl]-benzoesäure (Beispiel 19)
• – 3-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenylethinyl]-benzoesäure (Beispiel 20)
• – (8S,11R,13S,14S,17S)-17-Hydroxy-11-[4-(3-hydroxy-3-methyl-but-1-inyl)-phenyl]-13-methyl-17-pentafluorethyl-1,2,6,7,8,11,12,13,14,15,16,17-dodecahydro-cyclopenta[a]phenanthren-3-on (Beispiel 21)
• – (8S,11R,13S,14S,17S)-11-(4-Ethinyl-phenyl)-17-hydroxy-13-methyl-17-pentafluorethyl-1,2,6,7,8,11,12,13,14,15,16,17-dodecahydro-cyclopenta[a]phenanthren-3-on (Beispiel 22)
• – (8S,11R,13S,14S,17S)-11-[4-(3-Azido-prop-1-in-1-yl)-phenyl]-17-hydroxy-13-methyl-17-pentafluorethyl-1,2,6,7,8,11,12,13,14,15,16,17-dodecahydro-cyclopenta[a]phenanthren-3-on (Beispiel 23)
• – (E)-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-propinal O-benzyl-oxim (Beispiel 24A)
• – und (Z)-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-propinal O-benzyl-oxim (Beispiel 24B)
• – (E)-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-propinal O-ethyl-oxim (Beispiel 25A)
• – (Z)-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-propinal O-ethyl-oxim (Beispiel 25B)
• – [4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-propinal O-isobutyl-oxim (Beispiel 26)
• – [4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-propinal O-(3,4-dichlor-benzyl)-oxim (Beispiel 27)
• – 1-(3,5-Dimethyl-isoxazol-4-yl)-3-{3-[4-((8S,11R,13S,14S,17S)-17-hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyl}-harnstoff (Beispiel 28)
• – 1-{3-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyl}-3-isopropyl-harnstoff (Beispiel 29)
• – 3-(3-{3-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyl}-ureido)-propionsäureethylester (Beispiel 30)
• – 1-Ethyl-3-{3-[4-((8S,11R,13S,14S,17S)-17-hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyl}-harnstoff (Beispiel 31)
• – 1-{3-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyl}-3-(4-methoxy-phenyl)-harnstoff (Beispiel 32)
• – 1-{3-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyl}-3-(4-tert-butyl-phenyl)-harnstoff (Beispiel 33)
• – 1-{3-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyl}-3-phenyl-harnstoff (Beispiel 34)
• – 1-{3-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyl}-3-(4-chlor-phenyl)-harnstoff (Beispiel 35)
• – 1-{3-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyl}-3-(4-fluor-phenyl)-harnstoff (Beispiel 36)
• – 4-(3-{3-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyl}-ureido)-benzoesäureethylester (Beispiel 37)
• – 1-{3-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyl}-3-(4-methyl-phenyl)-harnstoff (Beispiel 38)
• – 1-Benzyl-3-{3-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyl}-harnstoff (Beispiel 39)
• – 1-{3-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyl}-3-tert-butyl-harnstoff (Beispiel 40)
• – 1-Allyl-3-{3-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyl}-harnstoff (Beispiel 41)
• – (3-{3-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyl}-ureido)-essigsäureethylester (Beispiel 42)
• – 1-{3-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyl}-3-(4-piperidin-1-yl-phenyl)-harnstoff (Beispiel 43)
• – Allyl-carbaminsäure 3-[4-((8S,11R,13S,14S,17S)-17-hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyl ester (Beispiel 44)
• – Ethyl-carbaminsäure 3-[4-((8S,11R,13S,14S,17S)-17-hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyl ester (Beispiel 45)
• – Phenyl-carbaminsäure 3-[4-((8S,11R,13S,14S,17S)-17-hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyl ester (Beispiel 46)
• – 4-Methylphenyl-carbaminsäure 3-[4-((8S,11R,13S,14S,17S)-17-hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyl ester (Beispiel 47)
• – 4-Fluorphenyl-carbaminsäure 3-[4-((8S,11R,13S,14S,17S)-17-hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyl ester (Beispiel 48)
• – Isopropyl-carbaminsäure 3-[4-((8S,11R,13S,14S,17S)-17-hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyl ester (Beispiel 49)
• – Benzyl-carbaminsäure 3-[4-((8S,11R,13S,14S,17S)-17-hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyl ester (Beispiel 50)
• – (8S,11R,13S,14S,17S)-17-Hydroxy-11-[4-(3-methanesulfonyl-phenylethinyl)-phenyl]-13-methyl-17-pentafluorethyl-1,2,6,7,8,11,12,13,14,15,16,17-dodecahydro-cyclopenta[a]phenanthren-3-on (Beispiel 51)
• – 4-Methoxyphenyl-carbaminsäure 3-[4-((8S,11R,13S,14S,17S)-17-hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyl ester (Beispiel 52)
• – 4-{3-[4-((8S,11R,13S,14S,17S)-17-Hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyloxycarbonylamino}-benzoesäureethylester (Beispiel 53)
• – (4-Piperidin-1-yl-phenyl)-carbaminsäure 3-[4-((8S,11R,13S,14S,17S)-17-hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyl ester (Beispiel 54)
• – 4-Chlorphenyl-carbaminsäure 3-[4-((8S,11R,13S,14S,17S)-17-hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyl ester (Beispiel 55)
• – (8S,11R,13S,14S,17S)-17-Hydroxy-11-[4-(4-methanesulfonyl-phenylethinyl)-phenyl]-13-methyl-17-pentafluorethyl-1,2,6,7,8,11,12,13,14,15,16,17-dodecahydro-cyclopenta[a]phenanthren-3-on (Beispiel 56)
• – 3-Pyridyl-carbaminsäure 3-[4-((8S,11R,13S,14S,17S)-17-hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyl ester (Beispiel 57)
• – tert-Butyl-carbaminsäure 3-[4-((8S,11R,13S,14S,17S)-17-hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyl ester (Beispiel 58)
• – 4-tert-Butylphenyl-carbaminsäure 3-[4-((8S,11R,13S,14S,17S)-17-hydroxy-13-methyl-3-oxo-17-pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)-phenyl]-prop-2-inyl ester (Beispiel 59)

Particularly preferred according to the invention are the compounds mentioned below whose preparation is described in the examples:

• - (8S, 11R, 13S, 14S, 17S) -17-hydroxy-11- [4- (3-hydroxyprop-1-yn-1-yl) -phenyl] -13-methyl-17-pentafluoroethyl-1 , 2,6,7,8,11,12,13,14,15,16,17-dodecahydro-cyclopenta [a] -phenanthren-3-one (Example 1)
• - [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13,14 , 15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -propynoic acid (Example 2)
• - [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13,14 , 15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -propynoic acid methyl ester (Example 3)
• - (E) -5- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11 , 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -pent-2-en-4-in-nitrile (Example 4)
• - (Z) -5- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11 , 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -pent-2-en-4-in-nitrile (Example 5)
• - (E) -5- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11 , 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -pent-2-en-4-ynic acid ethyl ester (Example 6)
• 7- (2E / Z, 4E / Z) - [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6 , 7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -hepta-2,4-diene-6-ynyl acid ethyl ester (Example 7)
• - {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12, 13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyloxy-acetic acid tert-butyl ester (Example 8)
• - {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12, Methyl 13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyloxyacetate (Example 9)
• - {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12, 13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyloxy} -acetic acid (Example 10)
• - (8S, 11R, 13S, 14S, 17S) -17-hydroxy-11- {4- [3- (2-hydroxy-ethoxy) -prop-1-yn-1-yl] -phenyl} -13-methyl -17-pentafluoroethyl-1,2,6,7,8,11,12,13,14,15,16,17-dodecahydro-cyclopenta [a] phenanthren-3-one (Example 11)
• - 3 - {(E / Z) -4- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7 , 8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -but-1-en-3-ynyl} -benzoic acid methyl ester (Example 12) )
• - 3 - {(E) -4- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7, 8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -but-1-en-3-ynyl} -benzoic acid (Example 13A)
• - 3 - {(Z) -4- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7, 8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -but-1-en-3-ynyl} -benzoic acid (Example 13B)
• - {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12, 13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyloxy} -acetonitrile (Example 14)
• - 4- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13 , 14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenylethynyl] -benzoic acid methyl ester (Example 15)
• - 4- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13 , 14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenylethynyl] benzoic acid (Example 16)
• - 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13 , 14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenylethynyl] -benzoic acid methyl ester (Example 17)
• - (8 S, 11 R, 13 S, 14 S, 17 S) -17-hydroxy-13-methyl-17-pentafluoroethyl-11- {4- [3- (1 H -tetrazol-5-ylmethoxy) -prop-1-yn-1 -yl] -phenyl} -1,2,6,7,8,11,12,13,14,15,16,17-dodecahydro-cyclopenta [a] -phenanthren-3-one (Example 18)
• 4- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl) -3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12, 13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenylethynyl] benzoic acid (Example 19)
• - 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13 , 14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenylethynyl] benzoic acid (Example 20)
• - (8S, 11R, 13S, 14S, 17S) -17-hydroxy-11- [4- (3-hydroxy-3-methylbut-1-ynyl) phenyl] -13-methyl-17-pentafluoroethyl-1 , 2,6,7,8,11,12,13,14,15,16,17-dodecahydro-cyclopenta [a] phenanthren-3-one (Example 21)
• - (8S, 11R, 13S, 14S, 17S) -11- (4-ethynylphenyl) -17-hydroxy-13-methyl-17-pentafluoroethyl-1,2,6,7,8,11,12,13 , 14,15,16,17-dodecahydro-cyclopenta [a] -phenanthren-3-one (Example 22)
• - (8S, 11R, 13S, 14S, 17S) -11- [4- (3-azido-prop-1-yn-1-yl) -phenyl] -17-hydroxy-13-methyl-17-pentafluoroethyl-1 , 2,6,7,8,11,12,13,14,15,16,17-dodecahydro-cyclopenta [a] phenanthren-3-one (Example 23)
• - (E) - [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8, -11,12 , 13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -propinal O-benzyl-oxime (Example 24A)
• - and (Z) - [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11, 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -propinal O-benzyl-oxime (Example 24B)
• - (E) - [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8, -11,12 , 13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -propinal O-ethyl-oxime (Example 25A)
• - (Z) - [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8, -11,12 , 13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -propinal O-ethyl-oxime (Example 25B)
• - [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13,14 , 15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -propinal O-isobutyl-oxime (Example 26)
• - [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13,14, 15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -propinal O- (3,4-dichloro-benzyl) -oxime (Example 27)
• 1- (3,5-dimethyl-isoxazol-4-yl) -3- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo 17-pentafluoroethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop-2- inyl} urea (Example 28)
• 1- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11, 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl} -3-isopropyl-urea (Example 29)
• - 3- (3- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8 , 11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl} -ureido) -propionic acid ethyl ester (Example 30)
• 1-ethyl-3- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7, 8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl} -urea (Example 31)
• 1- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11, 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl} -3- (4-methoxy-phenyl) -urea (example 32)
• 1- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11, 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop-2-ynyl} -3- (4-tert-butyl-phenyl) -urea (Example 33)
• 1- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11, 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl} -3-phenyl-urea (Example 34)
• 1- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11, 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl} -3- (4-chloro-phenyl) -urea (example 35)
• 1- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11, 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl} -3- (4-fluoro-phenyl) -urea (example 36)
• - 4- (3- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8 , 11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl} -ureido) -benzoic acid ethyl ester (Example 37)
• 1- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11, 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl} -3- (4-methyl-phenyl) -urea (example 38)
• 1-Benzyl-3- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7, 8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl} -urea (Example 39)
• 1- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11, 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl} -3-tert-butyl-urea (Example 40)
• 1-allyl-3- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7, 8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl} -urea (Example 41)
• - (3- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11 , 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop-2-ynyl} -ureido) -essigsäureethyles ter (Example 42)
• 1- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11, 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop-2-ynyl} -3- (4-piperidin-1-yl-phenyl) urea (Example 43)
• Allyl-carbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11, 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl ester (Example 44)
• Ethyl-carbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11, 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl ester (Example 45)
• Phenyl-carbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11, 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl ester (Example 46)
• 4-methylphenylcarbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8, 11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl ester (Example 47)
• 4-fluorophenylcarbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8, 11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl ester (Example 48)
• Isopropylcarbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11, 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl ester (Example 49)
• Benzylcarbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11, 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl ester (Example 50)
• - (8 S, 11 R, 13 S, 14 S, 17 S) -17-hydroxy-11- [4- (3-methanesulfonylphenylethynyl) -phenyl] -13-methyl-17-pentafluoroethyl-1,2,6,7,8 , 11,12,13,14,15,16,17-dodecahydro-cyclopenta [a] -phenanthren-3-one (Example 51)
• 4-methoxyphenylcarbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8, 11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl ester (Example 52)
• 4- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11, 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyloxycarbonylamino} -benzoic acid ethyl ester (Example 53)
• - (4-piperidin-1-yl-phenyl) -carbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2, 3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl ester (Example 54)
• 4-chlorophenylcarbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8, 11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl ester (Example 55)
• - (8 S, 11 R, 13 S, 14 S, 17 S) -17-hydroxy-11- [4- (4-methanesulfonylphenylethynyl) -phenyl] -13-methyl-17-pentafluoroethyl-1,2,6,7,8 , 11,12,13,14,15,16,17-dodecahydro-cyclopenta [a] phenanthren-3-one (Example 56)
• 3-pyridylcarbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8, 11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl ester (Example 57)
• Tert-butylcarbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8, 11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl ester (Example 58)
• 4-tert-butylphenylcarbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7, 8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl ester (Example 59)

The in the respective combinations or preferred combinations of Remains in the specified remainder definitions become independent of the respective specified combinations of the radicals as desired also replaced by remainders of other combinations.

Most preferred are combinations of two or more of the above preferred ranges.

The invention furthermore relates to a process for the preparation of the derivatives of the formula I according to the invention. Such derivatives can be prepared as shown in Scheme 1 by reacting a phenylsulfonate of the general formula II in which
R ^{1 'is} a perfluorinated C ₁ -C ₁₀ -alkyl group,
X 'is an oxygen atom, two alkoxy groups OR ⁷ , a C ₂ -C ₁₀ -alkylene-α, ω-dioxy group, which may be straight-chain or branched,
R ^{7 is} C ₁ -C ₄ -alkyl,
R ^{8 is} hydrogen,
R ^{9 is} a hydroxyl group, or
R ⁸ , R ⁹ together signify a bond,
palladium-catalyzed coupling reactions into a compound of the general formula I 'in which R ¹ , X', R ⁸ and R ^{9 have} the abovementioned meanings and if appropriate converts functionalities present in R ¹ and / or carries out further subsequent reactions and if appropriate from the group X liberates the group X in the meaning of oxygen and / or generates a double bond (R ⁸ , R ⁹ together form a bond) by elimination of water (R ⁸ = hydrogen, R ⁹ = hydroxyl group) and optionally the carbonyl group (X = oxygen) further functionalized (X = NOR ⁶ or an NNHSO ₂ R ⁶ group). Scheme 1

If R ⁸ and R ⁹ together represent a bond in the structure of the general formula I ', this represents the three possible double bond isomers I'-A, I'-B and I'-C, which are very different during the reactions described Relationships can arise to each other.

Some possible reaction sequences to compounds of general formula I 'are exemplified in more detail in Scheme 2. Scheme 2

The Reaction of compounds of the general formula II to give compounds of the general formulas VI, VIII or XII is carried out by palladium catalyzed coupling reactions according to those known in the art Methods. Typical embodiments can be found in the examples 1a, 15a, 17b and 19.

The Reaction of compounds of the general formula VI to give compounds the general formula VII is carried out (a) by reaction of the alcohol with isocyanates or (b) in two stages by preparation of the chloroformate and further reaction with amines according to those known in the art Methods. Typical comments on (a) can be found in the Examples 44a to 49a and to (b) in Examples 50, 52-55 and 57-59.

The reaction of compounds of the general formula IV to give compounds of the general formulas V is carried out with isocyanates according to the methods known to the person skilled in the art. Typical designs can be found in Examples 28-43.

The Reaction of compounds of the general formula VI to give compounds of the general formulas X takes place (a) either by direct oxidation or (b) by a two step oxidation to form the aldehyde the general formula IX and subsequent oxidation to X after, the Specialist methods known. For example, the direct is called Oxidation with Jones reagent. Typical comments on (b) can be found in Examples 2a and 2.

The Reaction of compounds of the general formula IX to give compounds of the general formulas XI is carried out according to those known in the art Methods. Typical embodiments can be found in the examples 24a-27a.

The Reaction of compounds of the general formula IX to give compounds of the general formulas XII is carried out according to those known in the art Methods. Typical embodiments can be found in the examples 4a, 6a, 7a and 12a.

The Reaction of compounds of the general formula IX to give compounds of the general formulas XIII is carried out according to those known in the art Methods. A typical implementation can be found in example 22a.

Unless already done by the described reactions, in the compounds of the general formulas III, IV, V, VI, VII, VIII, X, XI, XII, XIII optionally present kelves in X 'cleaved and / or, if R ⁸ the Meaning hydrogen and R ^{9 has} the meaning of hydroxyl, eliminating water. A typical embodiment is found in Examples 1 and 28.

So far the preparation of the starting compounds is not described here are, these are known in the art or analogous to known compounds or methods described herein (see also examples 1 b to 1 e).

The Preparation of the salts takes place in the usual way, by a solution of the compounds with the general chemical Formula I with the equivalent amount or a surplus a base or acid, optionally in solution located, offset, if necessary, the precipitate separates or works up the solution in the usual way.

The formulation of the pharmaceutical compositions based on the novel compounds is carried out in a conventional manner by the active ingredient with the commonly used in galenics carriers, fillers, Zerfallbeeinflussern, binders, humectants, lubricants, absorbents, diluents, Geschmackskorrigentien, colorants, etc. processed and converted into the desired application form. It is up Remington's Pharmaceutical Science, 15th ed Mack Publishing Company, East Pennsylvania (1980) to point.

The Compounds according to the invention can act systemically and / or locally. For this purpose can you in a suitable manner, such. Oral, intrauterine [är], intravaginal, parenteral, pulmonary, nasal, sublingual, lingual, buccal, rectal, dermal, transdermal, conjunctival, otic or as Implant or stent are applied.

Intrauterine [är] In particular, the application by means of IUS (intrauterine system) or IUD (intrauterine device). Intravaginal application can u. a. using IVR / VRS (intra vaginal ring / vaginal ring system) respectively.

Intrauterine or intravaginal application forms (cf., for example, US Pat. WO 01/47490 , in particular page 1, line 10 to page 5, line 13 and page 7, line 19 to page 58, line 6, or for vaginal rings: WO 06/010097 , in particular page 10, line 22 to page 14, line 28), the compounds according to the invention and nonsilicone and / or silicone polymers, in particular also siloxane-based elastomers (cf. WO 01/47490 , especially page 7, line 19 - page 15, line 15).

For These routes of administration can be the inventive Compounds are administered in suitable administration forms.

For oral administration are functioning according to the prior art quickly and / or modified compounds of the invention donating application forms containing the compounds of the invention in crystalline and / or amorphous and / or dissolved form, such as. As tablets (uncoated or coated tablets, for example, with enteric or delayed dissolving or insoluble coatings that control the release of the compound of the invention), rapidly disintegrating in the oral cavity tablets or films / wafers, films / lyophilisates, capsules (for example, Hart Soft gelatin capsules), dragees, granules, pellets, powders, emulsions, suspensions, aerosols or solutions.

The Parenteral administration can bypass a resorption step happen (eg intravenous, intraarterial, intracardiac, intraspinal or intralumbar) or with involvement of absorption (eg, intramuscular, subcutaneous, intracutaneous, percutaneous or intraperitoneal). Suitable for parenteral administration themselves as application forms u. a. Injection and infusion preparations in the form of solutions, suspensions, emulsions, lyophilisates or sterile powders.

For the other routes of administration are suitable for. B. Inhalation medicines (including powder inhalers, nebulizers), nasal drops, solutions, sprays; lingual, sublingual or buccal tablets to be administered, Films / wafers or capsules, suppositories, ear or eye preparations, Vaginal capsules, aqueous suspensions (lotions, shake mixtures), lipophilic suspensions, ointments, creams, transdermal therapeutic Systems (such as patches), milk, pastes, foams, Scattering powders, implants or stents.

The Compounds according to the invention can converted into the mentioned application forms become. This can be done in a conventional manner by mixing with inert, Non-toxic, pharmaceutically suitable excipients happen. These adjuvants include u. a. excipients (for example, microcrystalline cellulose, lactose, mannitol), Solvents (eg liquid polyethylene glycols), Emulsifiers and dispersing or wetting agents (for example sodium dodecylsulphate, Polyoxysorbitanoleate), binders (for example polyvinylpyrrolidone), synthetic and natural polymers (for example albumin), Stabilizers (eg antioxidants such as ascorbic acid), Dyes (eg inorganic pigments such as iron oxides) and flavor and / or scent remedies.

Another The present invention relates to medicaments which are at least a compound of the invention, usually together with one or more inert, non-toxic, pharmaceutical contain suitable excipients, as well as their use to the previously mentioned purposes.

Nevertheless it may be necessary, if necessary, of the quantities mentioned to deviate, depending on body weight, Application route, individual behavior towards the Active substance, method of preparation and time or interval, too which the application takes place. So it can in some cases be sufficient, with less than the aforementioned minimum quantity while in other cases the said upper limit must be exceeded. In case of application larger quantities may be recommended, this one in several single doses to distribute over the day.

The Percentages in the following tests and examples are provided not stated otherwise, weight percentages; Parts are parts by weight. Solvent ratios, dilution ratios and concentration data of liquid / liquid solutions each refer to the volume.

The The following examples serve to explain the invention without limiting it.

Example 1:

(8S, 11R, 13S, 14S, 17S) -17-hydroxy-11- [4- (3-hydroxy-prop-1-yn-1-yl) phenyl] -13-methyl-17-pentafluoroethyl-1, 2,6,7,8,11,12,13,14,15,16,17-dodecahydro-cyclopenta [a] phenanthrene-3-one

The solution of 200 mg (0.32 mmol) of the compound according to Example 1a in 10.4 ml of acetone was treated with 480 ml of a 4N hydrochloric acid and stirred for 20 minutes at 23 ° C. It was poured into a saturated sodium bicarbonate solution, extracted several times with ethyl acetate, dried the combined organic Ex Tracted over sodium sulfate and the residue obtained after filtration and removal of the solvent purified by chromatography. Isolated 133 mg (80%) of the title compound as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.58 (3H), 1.40-1.55 (2H), 1.71 to 1.85 (4H), 2.02 to 2.63 (11H) , 2.72 (1H), 4.43 (1H), 4.49 (2H), 5.79 (1H), 7.13 (2H), 7.36 (2H) ppm.

Example 1a:

(5R, 8S, 11R, 13S, 14S, 17S) -11- [4- (3-hydroxyprop-1-in-1-yl) phenyl] -5 ', 5', 13-trimethyl-17- (pentafluoroethyl) -1,2,3,4,6,7,8,11,12,13,14,15,16,17-tetradecahydro-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane ] -5.17-diol

The Solution of 34.4 g (39.6 mmol) of that shown in Example 1b Compound in 435 ml of tetrahydrofuran was mixed with 19.6 ml of piperidine, 4.58 g of tetrakis (triphenylphosphine) palladium (0), 11.7 ml of propargyl alcohol and heated to 80 ° C for 1 hour. One poured into a saturated one Ammonium chloride solution, extracted several times with ethyl acetate, washed the combined organic extracts with saturated Ammonium chloride and sodium chloride solution and dried over Sodium sulfate. The after filtration and solvent removal The residue obtained was purified by chromatography. Isolated 4.53 g (18%) of the title compound as a colorless foam.

Example 1b:

1,1,2,2,3,3,4,4,4-nonafluoro-butane-1-sulfonic acid 4 - ((5R, 8S, 11R, 13S, 14S, 17S) -5,17-dihydroxy-5 ' , 5 ', 13-trimethyl-17- (pentafluoroethyl) -1,2,3,4,6,7,8,11,12,13,14,15,16,17-tetradecahydro-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane] -11-yl) -phenyl ester

To a solution of 25 g (43 mmol) of that of Example 1c 590 ml of tetrahydrofuran were prepared at -10 ° C 26.4 ml of a 1.6 molar solution of n-butyllithium in Hexane added. The mixture was stirred for 30 minutes at 0 ° C, added with 15.5 ml of perfluorobutane-1-sulfonic acid fluoride and allowed to stir for a further 1.5 hours at 0 ° C. It was mixed with 10 ml of triethylamine, poured into a saturated Sodium bicarbonate solution and stirred for 16 hours at 23 ° C. 10 ml of triethylamine were added again extracted several times with diethyl ether. The combined organic Extracts were washed with saturated sodium chloride solution, dried over sodium sulfate and purified after filtration and solvent removed residue by Chromatography. 31.8 g (82%) of the title compound were isolated as a pale yellow foam.

Example 1c:

((5R, 8S, 11R, 13S, 14S, 17S) -11- (4-hydroxyphenyl) -5.17-dihydroxy-5 ', 5', 13-trimethyl-17- (pentafluoroethyl) -1,2,3 , 4,6,7,8,11,12,13,14,15,16,17-tetradecahydro-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane]

The solution of 90 g (96 mmol) of the compound according to Example 1d and 30.3 g of ammonium Formate in 600 ml of methanol was treated with a suspension of 6.5 g of palladium on activated carbon (10%) in 80 ml of methanol and stirred for 2 hours at 23 ° C. It was diluted with dichloromethane, filtered through Celite and concentrated. The residue was dissolved in ethyl acetate, washed with water and saturated sodium chloride solution and dried over sodium sulfate. The residue obtained after filtration and removal of the solvent was purified by crystallization. Isolated 53.3 g (95%) of the title compound as a colorless solid.

Example 1d:

((5R, 8S, 11R, 13S, 14S, 17S) -11- [4- (phenylmethoxy) phenyl] -5.17-dihydroxy-5 ', 5', 13-trimethyl-17- (pentafluoroethyl) -1, 2,3,4,6,7,8,11,12,13,14,15,16,17-tetradecahydro-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane]

Out 7.4 g of magnesium turnings and a solution of 80 g 1-bromo-4- (phenylmethoxy) benzene in 267 ml of tetrahydrofuran with heating to 50-80 ° C and optionally with the addition of an iodine crystal and / or catalytic amounts of 1,2-dibromoethane the Grignard reagent. It was cooled to 0 ° C, added 1.51 g of copper (I) chloride and the solution dripped of 50 g (102 mmol) of the compound prepared according to Example 1e in 500 ml of tetrahydrofuran. It was stirred for 16 hours at 23 ° C, poured into a saturated ammonium chloride solution and extracted several times with ethyl acetate. The combined organic Extracts were washed with saturated sodium chloride solution and dried over sodium sulfate. The after filtration and solvent removal The solid obtained was purified by crystallization and isolated 47.7 g (69%) of the title compound as a colorless solid.

Example 1e:

(5R, 8S, 10R, 13S, 14S, 17S) -17- (pentafluoroethyl) -5,10-epoxy-5 ', 5', 13-trimethyl-1,2,3,4,6,7,8, 12,13,14,15,16,17-tridecahydro-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane] -17-ol

The solution of 10.0 g (27 mmol) (5'R, 8'S, 10'R, 13'S, 14'S) -5,5,13'-trimethyl-1 ', 2', 6 ', 7', 8 ' , 12 ', 13', 14 ', 15', 16'-decahydro-17'H-spiro [1,3-dioxane-2,3 '- [5,10] epoxycyclopenta [a] phenanthrene] -17'- on, which is analogous to the one in Tetrahedron Lett. 26, 2069-2072 (1985) in 145 ml of dichloromethane was cooled to -70 ° C, treated with 11.1 ml of previously condensed pentafluoroiodoethane and slowly added dropwise 54 ml of a 1.5 molar solution of methyl lithium lithium bromide complex in diethyl ether to. After 1 hour, it was poured into water, extracted with dichloromethane, washed with water and sodium chloride solution, and dried over sodium sulfate. After filtration and removal of the solvent isolated 12.9 g (98%) of the title compound, which was further reacted without purification.

Example 2:

[4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13,14, 15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -propinsäure

The solution of 38 mg (61 .mu.mol) of the compound prepared according to Example 2a in 2 ml of tert-butanol and 1.4 ml of tetrahydrofuran was added under ice-bath cooling with 0.4 ml of 2-methyl-2-butene, 0.48 ml of water , 25.3 mg sodium dihydrogen phosphate monohydrate and 42.6 mg sodium chlorite. It was allowed to react for 1 hour, poured into water, saturated with sodium chloride and extracted several times with ethyl acetate. The combined organic extracts were dried over sodium sulfate and the residue obtained after filtration and removal of the solvent was purified by chromatography. 7.7 mg (24%) of the title compound were isolated as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.56 (3H), 1.35-1.55 (2H), 1.69 to 2.80 (15H), 4.39 (1H), 3.31 -3.93 (> 1H), 5.74 (1H), 7.13 (2H), 7.35 (2H) ppm.

Example 2a:

3- {4 - [(5R, 8S, 11R, 13S, 14S, 17S) -5.17-Dihydroxy-5 ', 5', 13-trimethyl-17- (pentafluoroethyl) -1,2,4,5, 6,7,8,11,12,13,14,15,16,17-tetradecahydro-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane] -11-yl] phenyl} propynal

The Solution of 2.0 g (3.2 mmol) of that shown in Example 1a Compound in 50 ml of dichloromethane was mixed with a few beads 4 Å molecular sieve, 560 mg N-methylmorpholine N-oxide, 85 mg of tetrapropylammonium peruthenate and stirred for 1.5 hours at 23 ° C. Purified by chromatography to isolate 1.44 g (72%) of the title compound as a colorless foam.

Example 3:

[4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13,14, 15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -propinsäuremethylester

The solution of 62 mg (120 .mu.mol) of the compound according to Example 2 in 1 ml of tetrahydrofuran was added at 3 ° C with 2.5 ml of an ethereal solution of diazomethane and stirred for 30 minutes. The residue obtained after removal of the solvent was purified by chromatography and isolated 18 mg (28%) of the title compound as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.57 (3H), 1.40-1.55 (2H), 1.74 to 1.86 (3H), 2.07 (1H), 2.22 (1H), 2.24-2.64 (9H), 2.71 (1H), 3.84 (3H), 4.46 (1H), 5.79 (1H), 7.21 (2H), 7.50 (2H) ppm.

Example 4

(E) -5- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11, 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] pent-2-en-4-innitril

In analogy to Example 1, 125 mg (0.2 mmol) of the compound A prepared according to Example 4a were reacted and isolated after working up and purification 51 mg (47%) of the title compound as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.58 (3H), 1.40 to 1.56 (2H), 1.73 to 1.87 (3H), 2.05 (1H), 2.08 (1H), 2.19-2.65 (10H), 2.72 (1H), 4.46 (1H), 5.78 (1H), 5.80 (1H), 6.69 (1H), 7.19 (2H), 7.40 (2H) ppm.

Example 4a

(2E) -5- {4 - [(5R, 8S, 11R, 13S, 14S, 17S) -5.17-Dihydroxy-5 ', 5', 13-trimethyl-17- (pentafluoroethyl) -1,2, 4,5,6,7,8,11,12,13,14,15,16,17-tetradecahydro-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane] -11-yl ] phenyl} pent-2-en-4-enynitrile (A) and (2Z) -5- {4 - [(5R, 8S, 11R, 13S, 14S, 17S) -5,17-dihydroxy-5 ', 5'', 13-trimethyl-17- (pentafluoroethyl) -1,2,4,5,6,7,8,11,12,13,14,15,16,17-tetradecahydro-spiro [cyclopenta [a] phenanthrene 3,2 '- [1,3] dioxane] -11-yl] phenyl} pent-2-en-4-enynitrile (B)

The Solution of 0.2 ml cyanomethanephosphonic acid diethyl ester in 5 ml of diethyl ether was added with 2.1 ml of a 0.6 molar Solution of bis (trimethylsilyl) sodium amide and stirred 30 minutes at 23 ° C. Then you dripped the solution of 500 mg (0.83 mmol) of Example 2a in 3.4 ml of diethyl ether and left 1 Hour react. It was poured into water, extracted several times with ethyl acetate and The combined organic extracts dried over sodium sulfate. The residue obtained after filtration and removal of the solvent Purified by chromatography. 125 mg (24%) were isolated the title compound A and 67 mg (13%) of the title compound B, respectively as a colorless foam.

Example 5

(Z) -5- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11, 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] pent-2-en-4-innitril

In analogy to Example 1, 10.5 mg (17 μmol) of the compound B prepared according to Example 4a were reacted and, after working up and purification, 6.8 mg (62%) of the title compound were isolated as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.64 (3H), 1.43 to 1.66 (2H), 1.77-1.92 (3H), 2.06 to 2.18 (2H) , 2.25-2.70 (9H), 2.77 (1H), 4.51 (1H), 5.70 (1H), 5.84 (1H), 6.56 (1H), 7.25 (2H), 7.52 (2H) ppm.

Example 6

(E) -5- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11, 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] pent-2-en-4-yn-oate

In analogy to Example 1, 56.2 mg (81 μmol) of the compound prepared according to Example 6a were reacted and isolated after working up and purification 24.9 mg (52%) of the title compound as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.63 (3H), 1.36 (3H), 1.45-1.64 (2H), 1.76 to 1.97 (3H), 2.06 -2.20 (2H), 2.27-2.87 (10H), 4.28 (2H), 4.50 (1H), 5.84 (1H), 6.34 (1H), 7.02 (1H), 7.22 (2H), 7.45 (2H) ppm.

Example 6a

Ethyl (2E) -5- {4 - [(5R, 8S, 11R, 13S, 14S, 17S) -5.17-dihydroxy-5 ', 5', 13-trimethyl-17- (pentafluoroethyl) -1, 2,4,5,6,7,8,11,12,13,14,15,16,17-tetradecahydro-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane] -11 -yl] phenyl} pent-2-en-4-ynoate

The Solution of 34.5 μl Triethylphosphonoacetat in 0.71 ml of tetrahydrofuran was treated with 7.6 mg of a 55% suspension of sodium hydride in white oil and stirred for 15 minutes at 23 ° C. Then the solution was dripped of 70 mg (0.11 mmol) of the compound prepared according to Example 2a in 1.4 ml of tetrahydrofuran and allowed to react for 1 hour. It was mixed with sodium bicarbonate solution, extracted several times with ethyl acetate and dried the combined organic Extracts over sodium sulfate. The after filtration and solvent removal The residue obtained was purified by chromatography. 56 mg (72%) of the title compound were isolated as a colorless foam.

Example 7

7- (2E / Z, 4E / Z) - [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6, 7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) phenyl] hepta-2,4-dien-6-inylsäureethylester

In analogy to Example 1 were reacted 11.2 mg (16 .mu.mol) of the compounds prepared according to Example 7a and isolated after work-up and purification, 6.0 mg (63%) of the isomeric title compounds as a pale yellow foam.
¹ H-NMR (CDCl _3): δ = 0.59 (3H), 1.31 (3H), 1.41 to 1.56 (2H), 1.73 to 1.86 (3H), 2.01 -2.15 (2H), 2.19-2.65 (9H), 2.72 (1H), 4.23 (2H), 4.45 (1H), 5.79 (1H), 5.94 -6.20 (2H), 6.53 + 6.74 (1H), 7.16 (2H), 7.30-7.45 + 7.86 (3H) ppm.

Example 7a

Ethyl (2E / Z, 4E / Z) -7- {4 - [(5R, 8S, 11R, 13S, 14S, 17S) -5,17-dihydroxy-5 ', 5', 13-trimethyl-17 - (pentafluoroethyl) -1,2,4,5,6,7,8,11,12,13,14,15,16,17-tetradecahydro-spiro [cyclopenta [a] phenanthrene-3,2 '- [1 , 3] dioxane] -11-yl] phenyl} hepta-2,4-dien-6-ynoate

The Solution of 101 mg of (E) -4- (diethoxy-phosphoryl) -but-2-enoic acid ethyl ester in 2.74 ml of tetrahydrofuran was added with 162 μl of a 1.6 molar solution of n-butyllithium in hexane and stirred 45 minutes at 23 ° C. Then cooled one to -78 ° C, the solution dripped off 70 mg (0.11 mmol) of the example 2a shown. connection in 1.42 ml of tetrahydrofuran, removed the cooling bath and let react for 1 hour. One poured into a saturated one Ammonium chloride solution, extracted several times with ethyl acetate and dried the combined organic extracts Sodium sulfate. The after filtration and solvent removal The residue obtained was purified by chromatography. Isolated 11 mg (14%) of the title compound as a colorless foam.

Example 8

{3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13 , 14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop-2-ynyloxy} -acetic acid tert-butyl ester

In analogy to Example 1, 50 mg (68 μmol) of the compound prepared according to Example 8a were reacted and, after work-up and purification, 31.3 mg (73%) of the title compound were isolated as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.58 (3H), 1.49 (11H), 1.74 to 1.86 (3H), 2.01 (1H), 2.07 (1H), 2.22-2.64 (9H), 2.72 (1H), 4.12 (2H), 4.44 (1H), 4.51 (2H), 5.79 (1H), 7.13 ( 2H), 7.37 (2H) ppm.

Example 8a

tert-Butyl - [(3- {4 - [(5R, 8S, 11R, 13S, 14S, 17S) -5.17-dihydroxy-5 ', 5', 13-trimethyl-17- (pentafluoroethyl) -1, 2,4,5,6,7,8,11,12,13,14,15,16,17-tetradecahydro-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane] -11 -yl] phenyl} prop-2-in-1-yl acetate) oxy]

The Solution of 200 mg (0.32 mmol) of that shown in Example 1a Compound in 2 ml of dichloromethane was treated with 0.26 ml of bromoacetic acid tert-butyl ester, 0.75 ml of a 50% potassium hydroxide solution, 4.25 mg of tetrabutylammonium hydrogen sulfate and stirred for 1 hour at 23 ° C. You diluted with water and dichloromethane, acidified by adding one 4 molar hydrochloric acid and extracted with dichloromethane. The combined organic extracts were dried over Sodium sulfate. The after filtration and solvent removal The residue obtained was purified by chromatography. Isolated 206 mg (87%) of the title compound as a colorless foam.

Example 9

{3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13 , 14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop-2-ynyloxy} -acetic acid methyl ester

In analogy to Example 1, 32.2 mg (46 μmol) of the compound prepared according to Example 9a were reacted and, after work-up and purification, 18.7 mg (68%) of the title compound were isolated as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.58 (3H), 1.39 to 1.56 (2H), 1.73 to 1.87 (3H), 2.06 (1H), 2.20 2.64 (10H), 2.71 (1H), 3.77 (3H), 4.26 (2H), 4.43 (1H), 4.51 (2H), 5.78 (1H), 7.13 (2H), 7.36 (2H) ppm.

Example 9a

Methyl - -1,2 [(5R, 8S, 11R, 13S, 14S, 17S) -5.17-dihydroxy-5 ', 5', 13-trimethyl-17- (pentafluoroethyl) - [(3- {4 4,5,6,7,8,11,12,13,14,15,16,17-tetradecahydro-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane] -11-yl ] phenyl} prop-2-in-1-yl acetate) oxy]

In By analogy with Example 8, 50 mg (80 μmol) of it were added Example 1a compound and isolated after work-up and Purification 32 mg (58%) of the title compound as a colorless foam.

Example 10

{3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13 , 14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop-2-ynyloxy} -acetic acid

In analogy to Example 1, 25 mg (37 .mu.mol) of the compound prepared according to Example 10a reacted and after working up and purification, 3.2 mg (15%) of the title compound were isolated as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.58 (3H), 1.69 to 1.56 (2H), 1.73 to 1.87 (3H), 2.01-2.11 (2H) , 2.19-2.64 (9H), 2.71 (1H), 4.30 (2H), 4.44 (1H), 4.54 (2H), 5.80 (1H), 7.14 (2H), 7.36 (2H) ppm.

Example 10a

[(3- {4 - [(5R, 8S, 11R, 13S, 14S, 17S) -5.17-Dihydroxy-5 ', 5', 13-trimethyl-17- (pentafluoroethyl) -1,2,4, 5,6,7,8,11,12,13,14,15,16,17-tetradecahydro-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane] -11-yl] phenyl } prop-2-in-1-yl acetic acid) oxy]

In By analogy with Example 8, 50 mg (80 μmol) of it were added Example 1a using bromoacetic acid methyl ester after work-up and purification, isolated 45 mg (83%) of the Title compound as a colorless foam.

Example 11

(8S, 11R, 13S, 14S, 17S) -17-hydroxy-11- {4- [3- (2-hydroxy-ethoxy) -prop-1-in-1-yl] phenyl} -13-methyl- 17-pentafluoroethyl-1,2,6,7,8,11,12,13,14,15,16,17-dodecahydro-cyclopenta [a] phenanthrene-3-one

In analogy to Example 1, 15 mg (22 μmol) of the compound prepared according to Example 11a were reacted and, after working up and purification, 8.4 mg (66%) of the title compound were isolated as a colorless oil.
¹ H-NMR (CDCl _3): δ = 0.58 (3H), 1.40 to 1.54 (2H), 1.74 to 1.85 (3H), 1.93 to 2.12 (3H) , 2.21-2.64 (9H), 2.72 (1H), 3.71 (2H), 3.80 (2H), 4.42 (2H), 4.44 (1H), 5.79 (1H), 7.13 (2H), 7.37 (2H) ppm.

Example 11a

(5R, 8S, 11R, 13S, 14S, 17S) -11- {4- [3- (2-hydroxyethoxy) prop-1-in-1-yl] phenyl} -5 ', 5', 13-trimethyl- 17- (pentafluoroethyl) -1,2,3,4,6,7,8,11,12,13,14,15,16,17-tetradecahydro-spiro [cyclopenta [a] phenanthrene-3,2 '- [ 1,3] dioxane] -5.17-diol

The Solution of 97 mg (0.13 mmol) of that shown in Example 8a Compound in 1.95 ml of toluene was added at -70 ° C. with 0.66 ml of a 1 molar solution of diisobutylaluminum hydride in toluene. After 1 hour, poured into water, acidified Addition of a 1 molar hydrochloric acid, extracted several times with ethyl acetate, washed with the combined organic extracts saturated sodium chloride solution and dried over Sodium sulfate. The after filtration and solvent removal The residue obtained was purified by chromatography. Isolated 50 mg (56%) of the title compound as a colorless foam.

Example 12

3 - {(E / Z) -4- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7 , 8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -but-1-en-3-ynyl} -benzoic acid methyl ester

In analogy to Example 1, 83.3 mg (0.11 mmol) of a mixture of the compounds prepared according to Example 12a were reacted and isolated after working up and purification 46.8 mg (65%) of the title compounds as a pale yellow foam.
¹ H-NMR (CDCl _3): δ = 0.61 (3H), 1.40 to 1.56 (2H), 1.73 to 1.88 (3H), 2.01-2.13 (2H) , 2.22-2.65 (9H), 2.73 (1H), 3.92 + 3.93 (3H), 4.46 (1H), 5.79 (1H), 5.98 + 6, 46 (1H), 6.72 + 7.05 (1H), 7.17 (2H), 7.36-8.05 (5H), 8.10 + 8.75 (1H) ppm.

Example 12a

3 - {(E / Z) -4- [4 - ((5R, 8S, 11R, 13S, 14S, 17S) -5.17-Dihydroxy-5 ', 5', 13-trimethyl-17-pentafluoroethyl-2 , 3,4,5,6,7,8,11,12,13,14,15,16,17-tetradecahydro-1H-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane ] -11-yl) -phenyl] -but-1-en-3-ynyl} -benzoic acid methyl ester

The Solution of 406 mg of 3-methoxycarbonyltriphenylphosphonium bromide in 2 ml of toluene was added at 3 ° C with 1.4 ml of a 0.6 molar solution of bis (trimethylsilyl) sodium amide in Toluene and stirred for 60 minutes at 23 ° C. Subsequently The solution of 100 mg (0.16 mmol) of the solution was added dropwise Example 2a in 2 ml of toluene and allowed 1 Hour react. It was poured into water, extracted several times with ethyl acetate and dried the combined organic extracts Sodium sulfate. The after filtration and solvent removal The residue obtained was purified by chromatography. 82 mg (67%) of the title compounds were isolated as colorless Foam.

Example 13 (A + B)

(A) 3 - {(E) -4- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6, 7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -but-1-en-3-ynyl} -benzoic acid and ( B) 3 - {(Z) -4- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7 , 8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -but-1-en-3-ynyl} -benzoic acid

The solution of 42 mg (65 .mu.mol) of the compound according to Example 12 in 0.68 ml of tetrahydrofuran was mixed with 0.29 ml of a 5% aqueous lithium hydroxide solution and stirred for 16 hours at 23 ° C. It was acidified by addition of a 1 molar hydrochloric acid, saturated with sodium chloride, extracted several times with diethyl ether and the combined organic extracts were dried over sodium sulfate. The residue obtained after filtration and removal of the solvent was purified by chromatography. In each case 8.1 mg (20%) of the title compounds were isolated as a colorless foam.
¹ H-NMR (CDCl ₃ ) of A: δ = 0.60 (3H), 1.42-1.54 (2H), 1.74-1.86 (3H), 2.07 (1H), 2 , 24-2.65 (10H), 2.74 (1H), 4.45 (1H), 5.81 (1H), 6.47 (1H), 7.06 (1H), 7.16 (2H ), 7.40 (2H), 7.46 (1H), 7.65 (1H), 8.03 (1H), 8.16 (1H) ppm.
¹ H-NMR (CDCl ₃ ) of B: δ = 0.51 (3H), 1.38-1.54 (2H), 1.72-1.86 (3H), 1.97-2.08 ( 2H), 2.16-2.63 (10H), 2.69 (1H), 4.43 (1H), 5.74 (1H), 6.01 (1H), 6.74 (1H), 7 , 15 (2H), 7.50 (1H), 7.54 (2H), 7.86 (1H), 8.05 (1H), 9.14 (1H) ppm.

Example 14

{3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13 , 14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop-2-ynyloxy} -acetonitrile

In analogy to Example 1, 104 mg (160 μmol) of the compound prepared according to Example 14a were reacted and, after working up and purification, 81 mg (93%) of the title compound were isolated as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.58 (3H), 1.38-1.56 (2H), 1.71 to 1.88 (3H), 2.05 (1H), 2.07 (1H), 2.18-2.65 (9H), 2.72 (1H), 4.43 (3H), 4.54 (2H), 5.79 (1H), 7.16 (2H), 7.39 (2H) ppm.

Example 14a

{3- [4 - ((5R, 8S, 11R, 13S, 14S, 17S) -5.17-Dihydroxy-5 ', 5', 13-trimethyl-17-pentafluoroethyl-2,3,4,5,6 , 7,8,11,12,13,14,15,16,17-tetradecahydro-1H-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane] -11-yl) -phenyl ] prop-2-ynyloxy} -acetonitrile

In By analogy with Example 8, 250 mg (0.40 mmol) of the example were used 1a, using bromoacetonitrile After working up and purification 186 mg (70%) of the Title compound as a colorless foam.

Example 15

4- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluorothyl-2,3,6,7,8,11,12,13, 14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) phenylethynyl] benzoate

In analogy to Example 1, 14 mg (19 .mu.mol) of the compound prepared according to Example 15a reacted and, after working up and purification, isolated 7.7 mg (63%) of the title compound as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.61 (3H), 1.38 to 1.57 (2H), 1.73 to 1.90 (3H), 2.08 (1H), 2.14 (1H), 2.20-2.68 (9H), 2.74 (1H), 3.92 (3H), 4.47 (1H), 5.80 (1H), 7.19 (2H), 7.46 (2H), 7.57 (2H), 8.01 (2H) ppm.

Example 15a

4- [4 - ((5R, 8S, 11R, 13S, 14S, 17S) -5.17-Dihydroxy-5 ', 5', 13-trimethyl-17-pentafluoroethyl-2,3,4,5,6, 7,8,11,12,13,14,15,16,17-tetradecahydro-1H-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane] -11-yl) -phenylethynyl] benzoate

The Solution of 50 mg (84 μmol) of the Example 15b represented compound in 8 ml of tetrahydrofuran was added with 14.4 mg of methyl 4-chlorobenzoate, 3.4 ml of triethylamine, Tetrakis (triphenylphosphine) palladium (0), 1.3 mg copper (I) iodide, 2.4 mg and stirred for 3 hours at 23 ° C. One narrowed and purified the residue by chromatography. Isolated were 25 mg (41%) of the title compound as a colorless foam.

Example 15b

(5R, 8S, 11R, 13S, 14S, 17S) -11- (4-ethynyl-phenyl) -5 ', 5', 13-trimethyl-17-pentafluoroethyl-1,2,3,4,6,7, 8,11,12,13,14,15,16,17-tetradecahydro-1H-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane] -5.17-diol

The Solution of 1.64 g (2.63 mmol) of that shown in Example 2a Compound in 30 ml of tetrahydrofuran was mixed with 2 ml of a 50% potassium hydroxide solution and stirred for 2 hours at 60 ° C. It was diluted with water, acidified by adding a 1 molar hydrochloric acid and extracted several times with ethyl acetate. The combined organic extracts were washed with saturated sodium bicarbonate solution and saturated sodium chloride solution and dried over Sodium sulfate. The after filtration and solvent removal The residue obtained was purified by chromatography. Isolated 1.34 g (86%) of the title compound as a colorless foam.

Example 16

4- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13, 14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) phenylethynyl] benzoic acid

In analogy to Example 1, 28 mg (38 μmol) of the compound prepared according to Example 16a were reacted and, after working up and purification, 17 mg (74%) of the title compound were isolated as a colorless foam.
¹ H-NMR (CD ₃ OD): δ = 0.60 (3H), 1.37-1.56 (2H), 1.71-1.84 (3H), 2.10 (1H), 2, 20-2,48 (5H), 2,56-2,73 (4H), 2,82 (1H), 4,55 (1H), 5,74 (1H), 7,27 (2H), 7, 45 (2H), 7.47 (2H), 7.91 (2H) ppm.

Example 16a

4- [4 - ((5R, 8S, 11R, 13S, 14S, 17S) -5.17-Dihydroxy-5 ', 5', 13-trimethyl-17-pentafluoroethyl-2,3,4,5,6, 7,8,11,12,13,14,15,16,17-tetradecahydro-1H-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane] -11-yl) -phenylethynyl] benzoic acid

In By analogy with Example 13, 28 mg (38 .mu.mol) of the according to Example 15a shown compound and isolated according to Workup and purification 26 mg (95%) of the title compound as colorless Foam.

Example 17

3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13, 14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) phenylethynyl] benzoate

In analogy to Example 1, 459 mg (690 μmol) of the compound prepared according to Example 17a are reacted and, after working up and purification, 307 mg (73%) of the title compound are isolated as a colorless foam.
¹ H-NMR (CD ₃ OD): δ = 0.60 (3H), 1.35-1.59 (2H), 1.70-1.84 (3H), 2.10 (1H), 2, 18-2,49 (5H), 2,55-2,75 (4H), 2,82 (1H), 4,55 (1H), 5,74 (1H), 7,26 (2H), 7, 36-7.49 (3H), 7.59 (1H), 7.93 (1H), 8.07 (1H) ppm.

Example 17a

3- [4 - ((5R, 8S, 11R, 13S, 14S, 17S) -5.17-Dihydroxy-5 ', 5', 13-trimethyl-17-pentafluoroethyl-2,3,4,5,6, 7,8,11,12,13,14,15,16,17-tetradecahydro-1H-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane] -11-yl) -phenylethynyl] benzoic acid

In By analogy with Example 13, 19 mg (26 .mu.mol) of the according to Example 17b shown compound and isolated according to Work-up and purification 18 mg (97%) of the title compound as colorless Foam.

Example 17b

3- [4 - ((5R, 8S, 11R, 13S, 14S, 17S) -5.17-Dihydroxy-5 ', 5', 13-trimethyl-17-pentafluoroethyl-2,3,4,5,6, 7,8,11,12,13,14,15,16,17-tetradecahydro-1H-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane] -11-yl) -phenylethynyl] benzoate

The Mixture of 2.3 mg bis-acetonitrile-palladium (II) chloride, 6 mg 2-dicyclohexylphosphino-2 ', 4', 6'-triisopropylphenyl and adding 82.5 mg of cesium carbonate in 0.75 ml of acetonitrile at 23 ° C with 17 ul of 3-chlorobenzoate and after 30 minutes with the solution of 75 mg (0.13 mmol) the compound according to Example 15b in 0.75 ml of acetonitrile. It was allowed to react for 2 hours at 70 ° C, added with water and extracted several times with ethyl acetate. The United organic extracts were dried over sodium sulfate and Cleans the product obtained after filtration and removal of the solvent Residue by chromatography. Isolated 19 mg (21%) of the title compound as a colorless foam.

Example 18

(8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-17-pentafluoroethyl-11- {4- [3- (1H-tetrazol-5-ylmethoxy) -prop-1-in-1 yl] phenyl} -1,2,6,7,8,11,12,13,14,15,16,17-dodecahydro-cyclopenta [a] phenanthrene-3-one

In analogy to Example 1, 426 mg (200 .mu.mol) of the compound prepared according to Example 18a were reacted and, after work-up and purification, 44 mg (37%) of the title compound were isolated as a colorless foam.
¹ H-NMR (CD ₃ OD): δ = 0.57 (3H), 1.36-1.56 (2H), 1.69-1.83 (3H), 2.09 (1H), 2, 16-2,47 (5H), 2,54-2,72 (4H), 2,80 (1H), 4,50-4,56 (3H), 4,99 (2H), 5,74 (1H ), 7.22 (2H), 7.33 (2H) ppm.

Example 18a

(5R, 8S, 11R, 13S, 14S, 17S) -5 ', 5', 13-trimethyl-17-pentafluoroethyl-11- {4- [3- (1H-tetrazol-5-ylmethoxy) prop-1- ynyl] -phenyl} -1,2,3,4,6,7,8,11,12,13,14,15,16,17-tetradecahydro-1H-spiro [cyclopenta [a] phenanthrene-3,2 ' - [1,3] dioxane] -5.17-diol

The Solution of 20 mg (30 .mu.mol) of the Example 14a represented compound in 0.4 ml of dimethylformamide was added with 10 mg sodium azide, 1 mg ammonium chloride and heated 16 hours to 120 ° C. It was poured into water and extracted several times Ethyl acetate, washed the combined organic extracts with water and saturated sodium chloride solution and dried over Sodium sulfate. The after filtration and solvent removal The residue obtained is purified by chromatography. Isolated 11.5 mg (54%) of the title compound as a colorless Foam.

Example 19

4- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13, 14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) phenylethynyl] benzoic acid

The solution of 1 g (1.31 mmol) of the compound according to Example 19a in 7 ml of acetonitrile was treated with 350 mg of tert-butyl 4-ethynylbenzoate, 364 μl of triethylamine, 11 mg of palladium dichloride, 34 mg of triphenylphosphine, 6 mg of copper (I) iodide and heated to 80 ° C for 2 hours. It was poured into a saturated ammonium chloride solution, extracted several times with ethyl acetate, the combined organic extracts were washed with saturated sodium chloride solution and dried over sodium sulfate. The residue obtained after filtration and removal of the solvent was purified by chromatography. Isolated 318 mg (36%) of the title compound as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.60 (3H), 1.36 to 1.55 (2H), 1.60 (9H), 1.74 to 1.87 (3H), 2.01 -2.14 (2H), 2.22-2.66 (9H), 2.74 (1H), 4.46 (1H), 5.80 (1H), 7.18 (2H), 7.47 (2H), 7.55 (2H), 7.96 (2H) ppm.

Example 19a

1,1,2,2,3,3,4,4,4-nonafluoro-butane-1-sulfonic acid 4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3- oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl ester

The Solution of 17.1 g (27.2 mmol) (5R, 8S, 11R, 13S, 14S, 17S) -11- (4-hydroxyphenyl) -5 ', 5', 13-trimethyl-17-pentafluoroethyl- 2,3,4,6,7,8,11,12,13,14,15,16,17-tetradecahydro-1H-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane] 5,17-diol in 380 ml of tetrahydrofuran is cooled to -3 ° C, added with 25.5 ml of a 1.6 molar solution of butyllithium in hexane and after 30 minutes with 9.78 ml of nonafluorobutanesulfonyl fluoride. It was stirred for 1.5 hours at 0 ° C, poured into saturated Sodium bicarbonate solution, extracted several times with Ethyl acetate, washed the combined organic extracts with water and saturated sodium chloride solution and dried over Sodium sulfate. The after filtration and solvent removal The residue obtained was purified by crystallization 18.6 g (89%) of the title compound were isolated as a colorless solid.

Example 20

3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13, 14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) phenylethynyl] benzoic acid

In analogy to Example 19, 2 g (2.62 mmol) of the compound prepared according to Example 19a were reacted using tert-butyl 3-ethynylbenzoate and, after work-up and purification, 478 mg (27%) of the title compound were isolated colorless foam.
¹ H-NMR (CDCl _3): δ = 0.61 (3H), 1.40-1.65 (2H), 1.60 (9H), 1.74-1.88 (3H), 2.02 -2.13 (2H), 2.22-2.67 (9H), 2.74 (1H), 4.47 (1H), 5.80 (1H), 7.18 (2H), 7.40 (1H), 7.46 (2H), 7.66 (1H), 7.94 (1H), 8.12 (1H) ppm.

Example 21

(8S, 11R, 13S, 14S, 17S) -17-hydroxy-11- [4- (3-hydroxy-3-methyl-but-1-ynyl) phenyl] -13-methyl-17-pentafluoroethyl-1, 2,6,7,8,11,12,13,14,15,16,17-dodecahydro-cyclopenta [a] phenanthrene-3-one

In analogy to Example 1, 103 mg (160 μmol) of the compound prepared according to Example 21a were reacted and, after working up and purification, isolated 57 mg (66%) of the title compound as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.57 (3H), 1.38-1.56 (2H), 1.61 (6H), 1.72 to 1.86 (3H), 2.03 (1H), 2.06 (1H), 2.08 (1H), 2.19-2.65 (9H), 2.71 (1H), 4.43 (1H), 5.79 (1H), 7.11 (2H), 7.34 (2H) ppm.

Example 21a

(5R, 8S, 11R, 13S, 14S, 17S) -11- [4- (3-hydroxy-3-methyl-but-1-ynyl) -phenyl] -5 ', 5', 13-trimethyl-17- pentafluoroethyl-2,3,4,6,7,8,11,12,13,14,15,16,17-tetradecahydro-1H-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane-5,17-diol

In Analogously to Example 1a, 500 mg (0.58 mmol) of 1,1,2,2,3,3,4,4,4-nonafluorobutane-1-sulfonic acid 4 - (5R, 8S, 11R, 13S, 14S , 17S) -5.17-dihydroxy-17-pentafluoroethyl-5 ', 5', 13-trimethyl-2,3,4,6,7,8,11,12,13,14,15,16,17- tetradecahydro-1H-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxan-11-yl) -phenyl ester using 2-methyl-but-3-yn-2-ol and isolated after work-up and purification 103 mg (27%) of the title compound as a colorless foam.

Example 22

(8S, 11R, 13S, 14S, 17S) -11- (4-ethynyl-phenyl) -17-hydroxy-13-methyl-17-pentafluoroethyl-1,2,6,7,8,11,12,13, 14,15,16,17-dodecahydro-cyclopenta [a] phenanthrene-3-one

In analogy to Example 1, 13 mg (22 .mu.mol) of the compound according to Example 22a were reacted and isolated after working up and purification 8 mg (74%) of the title compound as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.58 (3H), 1.41 to 1.55 (2H), 1.74 to 1.86 (3H), 2.07 (1H), 2.11 (1H), 2.21-2.64 (9H), 2.72 (1H), 3.06 1 (H), 4.44 (1H), 5.79 (1H), 7.14 (2H) , 7.41 (2H) ppm.

Example 22a

(5R, 8S, 11R, 13S, 14S, 17S) -11- [4-ethynyl-phenyl] -5 ', 5', 13-trimethyl-17-pentafluoroethyl-2,3,4,6,7,8, 11,12,13,14,15,16,17-tetradecahydro-1H-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxan-5,17-diol

The Solution of 1.64 g (2.63 mmol) of that shown in Example 2a Compound in 30 ml of tetrahydrofuran was mixed with 2 ml of a 50% aqueous potassium hydroxide solution and stirred for 2 hours at 60 ° C. They acidified by adding a 1 molar hydrochloric acid, extracted repeatedly with ethyl acetate, washed the combined organic extracts with saturated sodium bicarbonate and sodium chloride solution and dried over sodium sulfate. The after filtration and Solvent removed residue purified one by chromatography. Isolated 1.34 g (86%) of the title compound as a colorless foam.

Example 23

(8S, 11R, 13S, 14S, 17S) -11- [4- (3-azido-prop-1-in-1-yl) -phenyl] -17-hydroxy-13-methyl-17-pentafluoroethyl-1, 2,6,7,8,11,12,13,14,15,16,17-dodecahydro-cyclopenta [a] phenanthrene-3-one

In analogy to Example 1, 21.7 mg (33 μmol) of the compound prepared according to Example 23a were reacted and, after work-up and purification, 14.5 mg (80%) of the title compound were isolated as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.59 (3H), 1.38-1.56 (2H), 1.71 to 1.88 (3H), 2.07 (1H), 2.17 -2.64 (10H), 2.72 (1H), 4.14 (2H), 4.44 (1H), 5.79 (1H), 7.15 (2H), 7.39 (2H) ppm ,

Example 23a

(5R, 8S, 11R, 13S, 14S, 17S) -11- [4- (3-azido-prop-1-in-1-yl) phenyl] -17-pentafluoroethyl-5 ', 5', 13- trimethyl-1,2,3,4,6,7,8,11,12,13,14,15,16,17-tetradecahydro-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane-5,17-diol

The Solution of 150 mg (0.24 mmol) of that shown in Example 1a Compound in 3.6 ml of tetrahydrofuran was added at 3 ° C with 0.1 ml of diphenylphosphoryl azide, 42 ul of 1,8-diazabicyclo [5.4.0] undec-7-ene and allowed to react for 2 hours at 23 ° C. One staggered with water, extracted several times with ethyl acetate, washed the combined organic extracts with saturated sodium chloride solution and dried over sodium sulfate. The after filtration and Solvent removed residue purified one by chromatography. 114 g (73%) of the title compound were isolated as a colorless foam.

Example 24 (A + B)

(A) (E) - [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11 , 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -propinal O-benzyl-oxime and (B) (Z) - [4 - (( 8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13,14,15,16,17 -dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -propinal O-benzyl-oxime

The solution of 52 mg (71 mmol) of the compounds according to Example 24a in 1.2 ml of acetone was treated with 0.11 ml of 4N hydrochloric acid and stirred for 20 minutes at 23 ° C. 59 μl of triethylamine were added, the mixture was concentrated and the residue obtained after filtration and removal of the solvent was purified by chromatography. Isolated 14 mg (31%) of the title compound A and 14.5 mg (33%) of the title compound B each as a colorless foam.
¹ H-NMR (CDCl ₃ ) of A: δ = 0.57 (3H), 1.38-1.56 (2H), 1.70-1.88 (3H), 2.08 (1H), 2 , 12 (1H), 2.19-2.65 (9H), 2.71 (1H), 4.44 (1H), 5.20 (2H), 5.79 (1H), 7.16 (2H ), 7.30-7.47 (7H), 7.60 (1H) ppm.
¹ H-NMR _(CDCl3) of B: δ = 0.57 (3H), 1.38 to 1.57 (2H), 1.72-1.88 (3H), 2.07 (1H), 2 , 17-2.64 (10H), 2.71 (1H), 4.44 (1H), 5.26 (2H), 5.79 (1H), 6.93 (1H), 7.17 (2H ), 7.28-7.48 (7H) ppm.

Example 24a

(E / Z) - [4 - ((5R, 8S, 11R, 13S, 14S, 17S) -5.17-Dihydroxy-5 ', 5', 13-trimethyl-17-pentafluoroethyl-2,3,4, 5,6,7,8,11,12,13,14,15,16,17-tetradecahydro-1H-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane] -11-yl ) -phenyl] -propinal O-benzyl-oxime

The Solution of 10.8 mg O-benzylhydroxylamine in 1 ml of ethanol was added with 50 mg (80 .mu.mol) of Example 2a Compound, stirred for 2 hours at 23 ° C, concentrated and purified the residue by chromatography. Isolated 52 mg (89%) of the title compounds as colorless Foam.

Example 25 (A + B)

(A) (E) - [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11 , 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -propinal O-ethyl-oxime and (B) (Z) - [4 - (( 8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13,14,15,16,17 -dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -propinal O-ethyl-oxime

In analogy to Example 24, 47 mg (71 μmol) of the compounds prepared according to Example 25a were reacted and, after working up and purification, 9 mg (23%) of the title compound A and 12 mg (30%) of the title compound B were each obtained as a colorless foam.
¹ H-NMR _(CDCl3) of A: δ = 0.57 (3H), 1.30 (3H), 1.39 to 1.56 (2H), 1.71 to 1.87 (3H), 2 , 08 (1H), 2,12 (1H), 2,19-2,65 (9H), 2,72 (1H), 4,22 (2H), 4,44 (1H), 5,79 (1H ), 7.16 (2H), 7.43 (2H), 7.53 (1H) ppm.
¹ H-NMR _(CDCl3) of B: δ = 0.57 (3H), 1.34 (3H), 1.39 to 1.57 (2H), 1.71 to 1.87 (3H), 2 , 07 (1H), 2,17 (1H), 2,19-2,65 (9H), 2,72 (1H), 4,27 (2H), 4,44 (1H), 5,79 (1H ), 6.89 (1H), 7.17 (2H), 7.44 (2H) ppm.

Example 25a

(E / Z) - [4 - ((5R, 8S, 11R, 13S, 14S, 17S) -5.17-Dihydroxy-5 ', 5', 13-trimethyl-17-pentafluoroethyl-2,3,4, 5,6,7,8,11,12,13,14,15,16,17-tetradecahydro-1H-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane] -11-yl ) -phenyl] -propinal O-ethyl-oxime

In analogy to Example 24a, 50 mg (80 μmol) of the compound prepared according to Example 2a were reacted using O-ethylhydroxylamine and, after working up and purification, isolated 47 mg (88%) the title compounds as a colorless foam.

Example 26

(E / Z) - [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11, 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -propinal O-isobutyl-oxime

In analogy to Example 1 were reacted 60 mg (86 .mu.mol) of the compounds prepared according to Example 25a and isolated after work-up and purification 9.3 mg (18%) of the title compounds as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.57 (3H), 0.93 (6H), 1.39 to 1.56 (2H), 1.71 to 1.88 (3H), 1.95 -2.11 (2H), 2.13 (1H), 2.20-2.66 (9H), 2.72 (1H), 3.93 (2H), 4.44 (1H), 5.79 (1H), 7.16 (2H), 7.42 (2H), 7.55 + 6.86 (1H) ppm.

Example 26a

(E / Z) - [4 - ((5R, 8S, 11R, 13S, 14S, 17S) -5.17-Dihydroxy-5 ', 5', 13-trimethyl-17-pentafluoroethyl-2,3,4, 5,6,7,8,11,12,13,14,15,16,17-tetradecahydro-1H-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane] -11-yl ) -phenyl] -propinal O-isobutyloxime

In By analogy with Example 24a, 50 mg (80 .mu.mol) of the Example 2a compound using O-isobutylhydroxylamine and after work-up and purification, isolated 47 mg (84%) of the Title compounds as a colorless foam.

Example 27

(E / Z) - [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11, 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -propinal O- (3,4-dichloro-benzyl) -oxime

In analogy to Example 1, 71 mg (80 .mu.mol) of the compounds prepared according to Example 27a were reacted and isolated after working up and purification 26 mg (47%) of the title compounds as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.57 (3H), 1.39 to 1.56 (2H), 1.71 to 1.88 (3H), 2.05 (1H), 2.07 (1H), 2.18-2.66 (9H), 2.72 (1H), 4.44 (1H), 5.12 + 5.18 (2H), 5.79 (1H), 6.94 + 7.61 (1H), 7.12-7.28 (3H), 7.37-7.54 (4H) ppm.

Example 27a

(E / Z) - [4 - ((5R, 8S, 11R, 13S, 14S, 17S) -5.17-Dihydroxy-5 ', 5', 13-trimethyl-17-pentafluoroethyl-2,3,4, 5,6,7,8,11,12,13,14,15,16,17-tetradecahydro-1H-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane] -11-yl ) -phenyl] -propinal O- (3,4-dichlorobenzyl) oxime

In By analogy with Example 24a, 50 mg (80 .mu.mol) of the Example 2a compound using O- (3,4-dichloro-benzyl) -hydroxylamine and isolated after work-up 71 mg of the title compound as Crude.

Example 28

1- (3,5-dimethyl-isoxazol-4-yl) -3- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17 -pentafluorethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop-2-ynyl }-urea

The solution of 25.6 mg (38 .mu.mol) of the compound according to Example 28a in 1 ml of dichloromethane was treated with 5.8 mg of 3,5-dimethylisoxazol-4-ylisocyanate and stirred for 1 hour at 23 ° C. It was mixed with 57 .mu.l of a 4 molar solution of hydrogen chloride in dioxane and after 10 minutes with 31.7 .mu.l of triethylamine. The mixture was concentrated and the residue was purified by chromatography. Isolated, 15.2 mg (61%) of the title compound as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.56 (3H), 1.38 to 1.53 (2H), 1.70 to 1.87 (2H), 1.98-2.10 (2H) , 2.12-2.63 (9H), 2.16 (3H), 2.31 (3H), 2.71 (1H), 3.09 (1H), 4.20 (2H), 4.41 (1H), 5.23 (1H), 5.77 (1H), 6.17 (1H), 7.10 (2H), 7.27 (2H) ppm.

Example 28a

(5R, 8S, 11R, 13S, 14S, 17S) -11- [4- (3-amino-prop-1-in-1-yl) phenyl] -17-pentafluoroethyl-5 ', 5', 13- trimethyl-1,2,3,4,6,7,8,11,12,13,14,15,16,17-tetradecahydro-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane] -5.17-diol

The Solution of 267 mg (0.41 mmol) of that shown in Example 23a Compound in 10 ml of tetrahydrofuran was mixed with 2 ml of water, 1 ml of trimethylphosphine and stirred for 4 hours at 23 ° C. It was mixed with 1 ml of a 25% ammonia solution, stirred another 16 hours at 23 ° C and concentrated. The as raw product The title compound obtained was further reacted without purification.

Example 29

1- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12 , 13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop-2-ynyl} -3-isopropyl-urea

In analogy to Example 28, 35 mg (52 μmol) of the compound prepared according to Example 28a were reacted using isopropyl isocyanate and, after working up and purification, isolated 19.5 mg (62%) of the title compound as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.57 (3H), 1.11 (6H), 1.39 to 1.54 (2H), 1.72-1.87 (3H), 2.04 (1H), 2.18-2.64 (9H), 2.70 (1H), 3.40 (1H), 3.85 (1H), 4.14 (2H), 4.40 (1H), 4.74 (1H), 5.03 (1H), 5.77 (1H), 7.10 (2H), 7.30 (2H) ppm.

Example 30

3- (3- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8, 11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop-2-ynyl} -ureido) -propionic acid ethyl ester

In analogy to Example 28, 25 mg (37 μmol) of the compound prepared according to Example 28a were reacted using 3-isocyanato-propionic acid ethyl ester and, after working up and purification, isolated 16.7 mg (68%) of the title compound as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.57 (3H), 1.23 (3H), 1.37 to 1.54 (2H), 1.71 to 1.87 (3H), 2.05 (1H), 2.17-2.63 (11H), 2.71 (1H), 3.09 (1H), 3.45 (2H), 4.07-4.19 (4H), 4.41 (1H), 4.98 (1H), 5.29 (1H), 5.77 (1H), 7.11 (2H), 7.31 (2H) ppm.

Example 31

1-ethyl-3- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8 , 11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop-2-ynyl} -urea

In analogy to Example 28, 88 mg (0.11 mmol) of the compound prepared according to Example 28a were reacted using ethyl isocyanate and isolated after working up and purification 35 mg (43%) of the title compound as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.57 (3H), 1.12 (3H), 1.37 to 1.57 (2H), 1.71 to 1.89 (3H), 2.05 (1H), 2.16-2.65 (9H), 2.70 (1H), 2.82 (1H), 3.22 (2H), 4.17 (2H), 4.42 (1H), 4.60 (1H), 4.76 (1H), 5.78 (1H), 7.11 (2H), 7.32 (2H) ppm.

Example 32

1- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12 , 13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop-2-ynyl} -3- (4-methoxy-phenyl) -urea

In analogy to Example 28 were reacted 25 mg (37 .mu.mol) of the compound prepared according to Example 28a using 4-methoxyphenyl isocyanate and isolated after work-up and purification 12 mg (49%) of the title compound as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.55 (3H), 1.38-1.52 (2H), 1.71-1.86 (3H), 2.04 (1H), 2.17 -2.62 (9H), 2.69 (1H), 3.00 (1H), 3.75 (3H), 4.20 (2H), 4.39 (1H), 5.42 (1H), 5.77 (1H), 6.81 (2H), 6.88 (1H), 7.07 (2H), 7.18 (2H), 7.28 (2H) ppm.

Example 33

1- (3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12 , 13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop-2-ynyl} -3- (4-tert-butyl-phenyl) -urea

In analogy to Example 28, 25.6 mg (38 μmol) of the compound prepared according to Example 28a were reacted using 4-tert-butylphenyl isocyanate and isolated after working up and purification 11.8 mg (44%) of the title compound as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.55 (3H), 1.27 (9H), 1.38-1.52 (2H), 1.72 to 1.86 (3H), 2.04 (1H), 2.17-2.63 (9H), 2.69 (1H), 2.88 (1H), 4.22 (2H), 4.39 (1H), 5.52 (1H), 5.77 (1H), 6.95 (1H), 7.08 (2H), 7.20 (2H), 7.28 (2H), 7.30 (2H) ppm.

Example 34

1- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12 , 13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop-2-ynyl} -3-phenyl-urea

In analogy to Example 28, 25.6 mg (38 μmol) of the compound prepared according to Example 28a were reacted using phenyl isocyanate and, after working up and purification, isolated 12 mg (49%) of the title compound as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.55 (3H), 1.37-1.52 (2H), 1.72 to 1.86 (3H), 2.03 (1H), 2.16 -2,62 (9H), 2,68 (1H), 2,94 (1H), 4,21 (2H), 4,38 (1H), 5,67 (1H), 5,77 (1H), 7.08 (1H), 7.07 (2H), 7.19 (1H), 7.21-7.32 (6H) ppm.

Example 35

1- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12 , 13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop-2-ynyl} -3- (4-chloro-phenyl) -urea

In analogy to Example 28, 25 mg (37 μmol) of the compound prepared according to Example 28a were reacted using 4-chlorophenyl isocyanate and isolated after working up and purification 8.9 mg (35%) of the title compound as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.55 (3H), 1.39-1.52 (2H), 1.72 to 1.89 (3H), 2.04 (1H), 2.16 -2,62 (9H), 2,69 (1H), 2,87 (1H), 4,21 (2H), 4,39 (1H), 5,73 (1H), 5,77 (1H), 7.07 (2H), 7.17 (2H), 7.24 (2H), 7.26 (2H), 7.36 (1H) ppm.

Example 36

1- {3- [4 - ((8S, 11 R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12 , 13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop-2-ynyl} -3- (4-fluoro-phenyl) -urea

In analogy to Example 28, 25.6 mg (38 μmol) of the compound prepared according to Example 28a were reacted using 4-fluorophenyl isocyanate and, after working up and purification, isolated 13.3 mg (53%) of the title compound as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.55 (3H), 1.38 to 1.53 (2H), 1.72-1.87 (3H), 2.03 (1H), 2.16 -2,62 (9H), 2,69 (1H), 3,02 (1H), 4,19 (2H), 4,38 (1H), 5,71 (1H), 5,77 (1H), 6.90 (2H), 7.06 (2H), 7.20-7.27 (4H), 7.32 (1H) ppm.

Example 37

4- (3- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8, 11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop-2-ynyl} -ureido) -benzoic acid ethyl ester

In analogy to Example 28, 25 mg (37 μmol) of the compound prepared according to Example 28a were reacted using 4-isocyanato-benzoic acid ethyl ester and, after working up and purification, isolated 6.0 mg (23%) of the title compound as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.58 (3H), 1.36 (3H), 1.39-1.52 (2H), 1.72-1.87 (3H), 2.03 (1H), 2,17-2,63 (9H), 2,69 (1H), 3,30 (1H), 4,19-4,35 (4H), 4,38 (1H), 5,78 (1H), 6.06 (1H), 7.04 (2H), 7.21 (2H), 7.44 (2H), 7.83 (1H), 7.87 (2H) ppm.

Example 38

1- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12 , 13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop-2-ynyl} -3- (4-methyl-phenyl) -urea

In analogy to Example 28 were reacted 25 mg (37 .mu.mol) of the compound prepared according to Example 28a using 4-methylphenyl isocyanate and isolated after work-up and purification, 10.8 mg (44%) of the title compound as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.55 (3H), 1.37 to 1.54 (2H), 1.70-1.82 (3H), 2.04 (1H), 2.15 2.63 (9H), 2.28 (3H), 2.69 (1H), 2.90 (1H), 4.20 (2H), 4.39 (1H), 5.47 (1H), 5.77 (1H), 6.92 (1H), 7.07 (4H), 7.16 (2H), 7.28 (2H) ppm.

Example 39

1-benzyl-3- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8 , 11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop-2-ynyl} -urea

In analogy to Example 28 were reacted 35 mg (52 .mu.mol) of the compound prepared according to Example 28a using benzyl isocyanate and isolated after work-up and purification 17.5 mg (51%) of the title compound as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.56 (3H), 1.36 to 1.53 (2H), 1.70 to 1.98 (3H), 2.04 (1H), 2.14 -2,62 (9H), 2,67 (1H), 3,28 (1H), 4,11 (2H), 4,29 (2H), 4,38 (1H), 5,26 (1H), 5.37 (1H), 5.75 (1H), 7.08 (2H), 7.19-7.30 (7H) ppm.

Example 40

1- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12 , 13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop-2-ynyl} -3-tert-butyl-urea

In analogy to Example 28 were reacted 35 mg (52 .mu.mol) of the compound prepared according to Example 28a using tert-butyl isocyanate and isolated after work-up and purification, 12.6 mg (39%) of the title compound as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.57 (3H), 1.33 (9H), 1.37 to 1.56 (2H), 1.72-1.88 (3H), 2.05 (1H), 2.18-2.64 (9H), 2.64-2.78 (2H), 4.13 (2H), 4.41 (1H), 4.53 (1H), 4.63 (1H), 5.78 (1H), 7.10 (2H), 7.31 (2H) ppm.

Example 41

1-allyl-3- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8 , 11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop-2-ynyl} -urea

In analogy to Example 28, 25 mg (37 μmol) of the compound prepared according to Example 28a were reacted using allyl isocyanate and isolated after working up and purification 6.3 mg (28%) of the title compound as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.57 (3H), 1.38-1.56 (2H), 1.71 to 1.88 (3H), 2.05 (1H), 2.15 2.63 (9H), 2.70 (1H), 2.72 (1H), 3.81 (2H), 4.18 (2H), 4.41 (1H), 4.79 (1H), 4,88 (1H), 5,11 (1H), 5,20 (1H), 5,78 (1H), 5,84 (1H), 7,11 (2H), 7,32 (2H) ppm.

Example 42

(3- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11, 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop-2-ynyl} -ureido) -acetic acid ethyl ester

In analogy to Example 28, 35 mg (52 μmol) of the compound prepared according to Example 28a were reacted using isocyanatoacetic acid ethyl ester and, after working up and purification, isolated 17.1 mg (51%) of the title compound as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.56 (3H), 1.24 (3H), 1.36 to 1.56 (2H), 1.39 to 1.88 (3H), 2.05 (1H), 2.16-2.63 (9H), 2.70 (1H), 3.15 (1H), 3.98 (2H), 4.11-4.23 (4H), 4.40 (1H), 5.34 (1H), 5.46 (1H), 5.77 (1H), 7.10 (2H), 7.31 (2H) ppm.

Example 43

1- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12 , 13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop-2-ynyl} -3- (4-piperidin-1-yl-phenyl) - urea

In analogy to Example 28, 28 mg (38 μmol) of the compound prepared according to Example 28a were reacted using 4-piperidin-1-yl-phenyl isocyanate and isolated after working up and purification 8.4 mg (31%) of the title compound as colorless Foam.
¹ H-NMR (CDCl _3): δ = 0.56 (3H), 1.38 to 1.87 (11H), 2.05 (1H), 2.17 to 2.64 (9H), 2.68 (1H), 2.70 (1H), 3.12 (4H), 4.22 (2H), 4.40 (1H), 5.07 (1H), 5.78 (1H), 6.40 ( 1H), 6.89 (2H), 7.09 (2H), 7.13 (2H), 7.31 (2H) ppm.

Example 44

Allylcarbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12 , 13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl ester

In analogy to Example 1, 89 mg (80 .mu.mol) of the compound prepared according to Example 44a reacted and isolated after working up and purification 25 mg (52%) of the title compound as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.57 (3H), 1.40-1.55 (2H), 1.73 to 1.86 (3H), 2.07 (1H), 2.11 (1H), 2.21-2.65 (9H), 2.72 (1H), 3.84 (2H), 4.43 (1H), 4.87 (1H), 4.91 (2H), 5.14 (1H), 5.21 (1H), 5.79 (1H), 5.85 (1H), 7.13 (2H), 7.38 (2H) ppm.

Example 44a

Allylcarbamic acid 3- [4 - ((5R, 8S, 11R, 13S, 14S, 17S) -5,17-dihydroxy-17-pentafluoroethyl-5 ', 5', 13-trimethyl-2,3,4,5 , 6,7,8,11,12,13,14,15,16,17-tetradecahydro-1H-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane] -11-yl) -phenyl] -prop-2-ynyl ester

The Solution of 50 mg (80 .mu.mol) of Example 1a compound in 1.5 ml of dichloromethane was added with 424 μl allyl isocyanate and stirred for 3.5 days 23 ° C. One narrowed and put the residue without Continue cleaning.

Example 45

Ethyl carbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12 , 13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl ester

In analogy to Example 1, 27 mg (39 μmol) of the compound prepared according to Example 45a were reacted and, after work-up and purification, 12 mg (53%) of the title compound were isolated as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.57 (3H), 1.15 (3H), 1.38 to 1.57 (2H), 1.70-1.88 (3H), 2.06 (1H), 2.17-2.64 (10H), 2.71 (1H), 3.24 (2H), 4.43 (1H), 4.77 (1H), 4.88 (2H), 5.78 (1H), 7.13 (2H), 7.37 (2H) ppm.

Example 45a

Ethyl carbamic acid 3- [4 - ((5R, 8S, 11R, 13S, 14S, 17S) -5,17-dihydroxy-17-pentafluoroethyl-5 ', 5', 13-trimethyl-2,3,4,5 , 6,7,8,11,12,13,14,15,16,17-tetradecahydro-1H-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane] -11-yl) -phenyl] -prop-2-ynyl ester

In By analogy with Example 44a, 50 mg (80 .mu.mol) of the Example 1a compound using ethyl isocyanate at 60 ° C and isolated after work-up and purification 27 mg (48%) of the title compound as a colorless foam.

Example 46

Phenyl-carbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12 , 13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl ester

In analogy to Example 1, 53.4 mg (72 μmol) of the compound prepared according to Example 46a were reacted and, after working up and purification, 17.4 mg (38%) of the title compound were isolated as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.57 (3H), 1.40-1.55 (2H), 1.73-1.85 (3H), 2.06 (1H), 2.18 2.64 (10H), 2.71 (1H), 4.43 (1H), 5.00 (2H), 5.79 (1H), 6.80 (1H), 7.08 (1H), 7.13 (2H), 7.31 (2H), 7.37 (2H), 7.39 (2H) ppm.

Example 46a

Phenylcarbamic acid 3- [4 - ((5R, 8S, 11R, 13S, 14S, 17S) -5,17-dihydroxy-17-pentafluoroethyl-5 ', 5', 13-trimethyl-2,3,4,5 , 6,7,8,11,12,13,14,15,16,17-tetradecahydro-1H-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane] -11-yl) -phenyl] -prop-2-ynyl ester

In By analogy with Example 44a, 50 mg (80 .mu.mol) of the Example 1a compound using phenyl isocyanate After work-up and purification, 53 mg (90%) of the title compound were isolated as a colorless foam.

Example 47

4-Methylphenylcarbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11 , 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl ester

In analogy to Example 1, 25 mg (33 μmol) of the compound prepared according to Example 47a were reacted and, after working up and purification, 8.2 mg (38%) of the title compound were isolated as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.57 (3H), 1.38-1.56 (2H), 1.71-1.86 (3H), 2.07 (1H), 2.11 (1H), 2.18-2.66 (9H), 2.31 (3H), 2.71 (1H), 4.43 (1H), 4.99 (2H), 5.79 (1H), 6,66 (1H), 7,11 (2H), 7,14 (2H), 7,27 (2H), 7,38 (2H) ppm.

Example 47a

4-Methylphenylcarbamic acid 3- [4 - ((5R, 8S, 11R, 13S, 14S, 17S) -5,17-dihydroxy-17-pentafluoroethyl-5 ', 5', 13-trimethyl-2,3,4 , 5,6,7,8,11,12,13,14,15,16,17 tetradecahydro-1H-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane] -11- yl) -phenyl] -prop-2-ynyl ester

In By analogy with Example 44a, 50 mg (80 .mu.mol) of the Compound prepared according to Example 1a using 4-methylphenyl isocyanate and after work-up and purification, isolated 25 mg (42%) of the Title compound as a colorless foam.

Example 48

4-Fluorophenylcarbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11 , 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl ester

In analogy to Example 1, 157 mg (80 .mu.mol) of the compound prepared according to Example 48a were reacted and, after working up and purification, 9.2 mg (18%) of the title compound were isolated as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.57 (3H), 1.39 to 1.55 (2H), 1.74 to 1.85 (3H), 2.07 (1H), 2.10 (1H), 2.20-2.64 (9H), 2.71 (1H), 4.44 (1H), 5.00 (2H), 5.79 (1H), 6.72 (1H), 7.01 (2H), 7.14 (2H), 7.35 (2H), 7.38 (2H) ppm.

Example 48a

4-Fluorophenylcarbamic acid 3- [4 - ((5R, 8S, 11R, 13S, 14S, 17S) -5,17-dihydroxy-17-pentafluoroethyl-5 ', 5', 13-trimethyl-2,3,4 , 5,6,7,8,11,12,13,14,15,16,17-tetradecahydro-1H-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane] -11- yl) -phenyl] -prop-2-ynyl ester

In By analogy with Example 44a, 50 mg (80 .mu.mol) of the Compound prepared according to Example 1a using 4-fluorophenyl isocyanate and isolated the title compound as a crude product, without purification continues to be implemented.

Example 49

Isopropylcarbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12 , 13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl ester

In analogy to Example 1, 31.7 mg (45 μmol) of the compound prepared according to Example 49a were reacted and, after working up and purification, 15.5 mg (57%) of the title compound were isolated as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.57 (3H), 1.16 (6H), 1.38 to 1.57 (2H), 1.70 to 1.87 (3H), 2.06 (1H), 2.17-2.64 (10H), 2.71 (1H), 3.82 (1H), 4.42 (1H), 4.64 (1H), 4.87 (2H), 5.78 (1H), 7.12 (2H), 7.37 (2H) ppm.

Example 49a

Isopropylcarbamic acid 3- [4 - ((5R, 8S, 11R, 13S, 14S, 17S) -5,17-dihydroxy-17-pentafluoroethyl-5 ', 5', 13-trimethyl-2,3,4,5 , 6,7,8,11,12,13,14,15,16,17-tetradecahydro-1H-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane] -11-yl) -phenyl] -prop-2-ynyl ester

In By analogy with Example 44a, 50 mg (80 .mu.mol) of the Example 1a according to the invention using isopropyl isocyanate and isolated after work-up and purification 31.7 mg (56%) of Title compound as a colorless foam

Example 50

Benzylcarbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12 , 13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl ester

The solution of 39 mg (57 .mu.mol) of the compound according to Example 50a in 0.5 ml of dichloromethane was treated with the solution of 12.4 ul of benzylamine in 0.5 ml of dichloromethane and stirred for 1 hour at 23 ° C. It was mixed with water, extracted several times with dichloromethane and the combined organic extracts were dried over sodium sulfate. The residue obtained after filtration and removal of the solvent was purified by chromatography. Isolated, 5 mg (13%) of the title compound as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.57 (3H), 1.42-1.55 (2H), 1.74 to 1.87 (3H), 2.03-2.11 (2H) , 2.20-2.66 (9H), 2.72 (1H), 4.40 (2H), 4.43 (1H), 4.94 (2H), 5.11 (1H), 5.79 (1H), 7,13 (2H), 7,27-7,41 (7H) ppm.

Example 50a

Chloroformic acid 3- [4 - ((5R, 8S, 11R, 13S, 14S, 17S) -5,17-dihydroxy-5 ', 5', 13-trimethyl-17-pentafluoroethyl-2,3,4,5,6 , 7,8,11,12,13,14,15,16,17-tetradecahydro-1H-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane] -11-yl) -phenyl ] -prop-2-ynyl ester

The Solution of 50 mg (80 .mu.mol) of Example 1a compound in 0.5 ml of dichloromethane was added 0 ° C with 12.9 μl of pyridine, 23.8 mg of triphosgene and stirred for 1.5 hours. It is filtered through a little silica gel, the filtrate was concentrated and the title compound obtained without Continue cleaning.

Example 51

(8S, 11R, 13S, 14S, 17S) -17-hydroxy-11- [4- (3-Methanesulfonyl-phenylethynyl) phenyl] -13-methyl-17-pentafluoroethyl-1,2,6,7,8, 11,12,13,14,15,16,17-dodecahydro-cyclopenta [a] phenanthrene-3-one

In analogy to Example 1 were reacted 23 mg (31 .mu.mol) of the compound according to Example 50a shown compound and isolated after work-up and purification 10 mg (51%) of the title compound as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.61 (3H), 1.40 to 1.56 (2H), 1.74-1.88 (3H), 2.08 (1H), 2.18 (1H), 2.22-2.67 (9H), 2.74 (1H), 3.08 (3H), 4.47 (1H), 5.80 (1H), 7.20 (2H), 7.46 (2H), 7.56 (1H), 7.77 (1H), 7.89 (1H), 8.10 (1H) ppm.

Example 51a

(5R, 8S, 11R, 13S, 14S, 17S) -11- [4- (3-Methanesulfonyl-phenylethynyl) -phenyl] -5 ', 5', 13-trimethyl-17-pentafluoroethyl-1,2,3, 4,6,7,8,11,12,13,14,15,16,17-tetradecahydro-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane] -5.17-diol

In By analogy with Example 17b, 50 mg (84 μmol) of the Example 15b compound using 3-Bromophenyl methylsulfone and isolated after work-up and Purification 23 mg (37%) of the title compound as a colorless foam.

Example 52

4-Methoxyphenylcarbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11 , 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl ester

In analogy to Example 50, 52 mg (79 μmol) of the compound prepared according to Example 50a were reacted using p-anisidine and, after working up and purification, isolated 13 mg (25%) of the title compound as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.56 (3H), 1.38-1.56 (2H), 1.72 to 1.86 (3H), 2.07 (1H), 2.17 (1H), 2.19-2.64 (9H), 2.71 (1H), 3.78 (3H), 4.43 (1H), 4.99 (2H), 5.79 (1H), 6.63 (1H), 6.85 (2H), 7.13 (2H), 7.29 (2H), 7.38 (2H) ppm.

Example 53

4- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12 , 13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop-2-inyloxycarbonylamino} -benzoic acid ethyl ester

In analogy to Example 50, 46.7 mg (80 μmol) of the compound prepared according to Example 50a were reacted using ethyl 4-aminobenzoate and, after work-up and purification, 7.7 mg (14%) of the title compound were obtained as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.56 (3H), 1.38 (3H), 1.39 to 1.55 (2H), 1.72 to 1.86 (3H), 2.06 (1H), 2.18-2.64 (10H), 2.72 (1H), 4.35 (2H), 4.43 (1H), 5.02 (2H), 5.79 (1H), 7.03 (1H), 7.13 (2H), 7.37 (2H), 7.47 (2H), 8.00 (2H) ppm.

Example 54

(4-piperidin-1-yl-phenyl) -carbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3 , 6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl ester

In analogy to Example 50, 46.7 mg (80 μmol) of the compound prepared according to Example 50a were reacted using 4-piperidin-1-yl-phenylamine and, after working up and purification, isolated 10.1 mg (17%) of the title compound as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.56 (3H), 1.38 to 1.87 (11H), 2.06 (1H), 2.17 (1H), 2.20 to 2.64 (9H), 2.72 (1H), 3.08 (4H), 4.43 (1H), 4.98 (2H), 5.79 (1H), 6.58 (1H), 6.90 ( 2H), 7,13 (2H), 7,25 (2H), 7,38 (2H) ppm.

Example 55

4-Chlorophenylcarbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11 , 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl ester

In analogy to Example 50, 46.7 mg (80 μmol) of the compound prepared according to Example 50a were reacted using 4-chloroaniline and, after working up and purification, isolated 7.4 mg (14%) of the title compound as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.56 (3H), 1.38 to 1.55 (2H), 1.72 to 1.86 (3H), 2.06 (1H), 2.09 (1H), 2.18-2.64 (9H), 2.71 (1H), 4.43 (1H), 5.00 (2H), 5.79 (1H), 6.76 (1H), 7.13 (2H), 7.27 (2H), 7.35 (2H), 7.38 (2H) ppm.

Example 56

(8S, 11R, 13S, 14S, 17S) -17-hydroxy-11- [4- (4-Methanesulfonyl-phenylethynyl) phenyl] -13-methyl-17-pentafluoroethyl-1,2,6,7,8, 11,12,13,14,15,16,17-dodecahydro-cyclopenta [a] phenanthrene-3-one

In analogy to Example 1, 11.4 mg (15 .mu.mol) of the compound prepared according to Example 56a were reacted and, after work-up and purification, 5.4 mg (55%) of the title compound were isolated as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.60 (3H), 1.42-1.56 (2H), 1.75-1.88 (3H), 2.08 (2H), 2.23 -2.67 (9H), 2.74 (1H), 3.07 (3H), 4.47 (1H), 5.80 (1H), 7.21 (2H), 7.48 (2H), 7.69 (2H), 7.92 (2H) ppm.

Example 56a

(5R, 8S, 11R, 13S, 14S, 17S) -11- [4- (4-Methanesulfonyl-phenylethynyl) -phenyl] -5 ', 5', 13-trimethyl-17-pentafluoroethyl-1,2,3, 4,6,7,8,11,12,13,14,15,16,17-tetradecahydro-spiro [cyclopenta [a] phenanthrene-3,2 '- [1,3] dioxane] -5.17-diol

In By analogy with Example 17b, 50 mg (84 μmol) of the Example 15b compound using 4-bromophenyl methylsulfone and isolated after work-up and Purification 11.4 mg (18%) of the title compound as a colorless foam.

Example 57

3-Pyridylcarbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11 , 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl ester

In analogy to Example 50, 93.3 mg (0.16 mmol) of the compound prepared according to Example 50a were reacted using pyridin-3-ylamine and isolated after working up and purification 16.3 mg (16%) of the title compound as colorless Foam.
¹ H-NMR (CDCl _3): δ = 0.57 (3H), 1.38 to 1.55 (2H), 1.72-1.87 (3H), 2.06 (1H), 2.17 2.63 (9H), 2.70 (1H), 3.10 (1H), 4.41 (1H), 5.02 (2H), 5.78 (1H), 7.10 (2H), 7.20 (1H), 7.28 (1H), 7.35 (2H), 8.02 (1H), 8.31 (1H), 8.49 (1H) ppm.

Example 58

tert -Butyl-carbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11 , 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl ester

In analogy to Example 50, 52 mg (79 μmol) of the compound prepared according to Example 50a were reacted using tert-butylamine, and after working up and purification, 16 mg (33%) of the title compound were isolated as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.57 (3H), 1.33 (9H), 1.40 to 1.54 (2H), 1.73-1.85 (3H), 2.07 (1H), 2.17 (1H), 2.20-2.64 (9H), 2.72 (1H), 4.43 (1H), 4.77 (1H), 4.85 (2H), 5.79 (1H), 7.13 (2H), 7.37 (2H) ppm.

Example 59

4-tert-butylphenylcarbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8 , 11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl ester

In analogy to Example 50, 46.7 mg (80 μmol) of the compound prepared according to Example 50a were reacted using 4-tert-butylaniline and, after working up and purification, isolated 11 mg (19%) of the title compound as a colorless foam.
¹ H-NMR (CDCl _3): δ = 0.57 (3H), 1.30 (9H), 1.40 to 1.54 (2H), 1.73-1.85 (3H), 2.02 -2.12 (2H), 2.20-2.63 (9H), 2.72 (1H), 4.44 (1H), 5.00 (2H), 5.79 (1H), 6.67 (1H), 7.13 (2H), 7.30 (2H), 7.34 (2H), 7.38 (2H) ppm.

Example 60

Determination of progesterone receptor antagonist Effect in stable, transfectant human neuroblastoma cells (SK-N-MC cells) with human progesterone A or progesterone B receptor and a MN-LUC reporter construct

• a) agonistische Aktivitat: Keine der genannten Verbindungen zeigt eine agonistische Aktivitat.
• b) antagonistische Aktivitat: Alle genannten Verbindungen zeigen eine 100%ige antagonistische Wirksamkeit. Die antagonistische Wirkstärke der Verbindungen ist in Tabelle 1 zusammengefasst. Erfindungsgemäß bevorzugt sind Verbindungen deren PR-A oder PR-B Wert ≤ 0,2 nM ist.

Bsp. IC₅₀ [nM] Bsp. IC₅₀ [nM] Bsp IC₅₀ [nM] PR-A PR-B PR-A PR-B PR-A PR-B 1 0,097 0,11 21 0,36 1,0 40 0,1 0,3 2 32 16 22 0,014 0,014 41 0,1 0,1 3 1,8 1,2 23 0,2 0,3 42 0,7 0,8 4 0,2 0,1 24A 0,1 0,1 43 0,8 0,9 5 0,72 0,76 24B 0,1 0,1 44 0,01 0,01 6 13 12 25A 0,01 0,08 45 0,01 0,01 7 0,8 0,9 25B 0,09 0,09 46 0,01 0,01 8 0,32 0,41 26 0,08 0,08 47 0,01 0,01 9 8,1 10 27 0,97 2,0 48 0,09 0,08 10 9,0 10 28 0,04 0,08 49 0,01 0,07 11 0,32 1,0 29 0,1 0,1 50 0,01 0,03 12 1 2 30 0,1 0,4 51 0,08 0,1 13A 0,1 0,2 31 0,08 0,1 52 0,01 0,07 13B nd nd 32 0,2 0,1 53 0,16 0,19 14 0,1 0,1 33 0,9 0,8 54 0,10 0,09 15 0,7 1,0 34 0,1 0,1 55 0,26 0,2 16 0,1 0,05 35 0,4 0,4 56 0,01 0,08 17 0,2 0,2 36 0,1 0,2 57 0,01 0,08 18 8 5 37 0,1 0,4 58 0,09 0,01 19 3,3 4,3 38 0,2 0,3 59 0,7 1,2 20 2,3 7,0 39 0,1 0,1 Ref. 1* 0,4 0,3 Tabelle 1

• nd = nicht ermittelt
• * Ref. 1 Tabelle 1: Als Vergleichsverbindung (Referenzsubstanz) dient die in Beispiel 10 der WO 1998/34947 beschriebene Verbindung (8S,11R,13S,14S,17S)-17-Hydroxy-11-[4-(hydroxymethyl)-phenyl]-13-methyl-17-pentafluorethyl-1,2,6,7,8,11,12,13,14,15,16,17-dodecahydro-cyclopenta[a]phenanthren-3-on.

SK-N-MC cells (human neuroblastoma cells) stably transfected with plasmids containing human progesterone receptor B (pRChPR-B-neo) or human progesterone receptor A (pRChPR-A-neo) and a reporter construct (pMMTV -LUC) were incubated for 24 hours either in the absence (negative control) or in the presence of increasing amounts of the respective test compound (0.01 nmol / l, 0.1 nmol / l, 1 nmol / l, 10 nmol / l, 100 nmol / l and 1 pmol / l) to determine agonist activity. As a positive control of reporter gene induction, the cells were treated with the synthetic progestin Promegeston (0.01 nmol / l, 0.1 nmol / l, 1 nmol / l, 10 nmol / l, 100 nmol / l and 1 pmol / l). To determine the antagonistic activity, the cells were incubated with 0.1 nmol / l promegestone and additionally with increasing amounts of the respective test compound (0.01 nmol / l, 0.1 nmol / l, 1 nmol / l, 10 nmol / l, 100 nmol / l and 1 pmol / l). The activity of the reporter gene LUC (LUC = luciferase) was determined in the cell lysates and measured as RLU (relative light units). All measured values are given as% effectiveness and as EC ₅₀ or IC ₅₀ concentrations.

• a) agonistic activity: None of the compounds mentioned show an agonistic activity.
• b) antagonistic activity: All the compounds mentioned show a 100% antagonistic activity. The antagonistic potency of the compounds is summarized in Table 1. Preferred compounds according to the invention are compounds whose PR-A or PR-B value is ≦ 0.2 nM.

Ex. IC ₅₀ [nM] Ex. IC ₅₀ [nM] Example IC ₅₀ [nM] PRE PR-B PRE PR-B PRE PR-B 1 0.097 0.11 21 0.36 1.0 40 0.1 0.3 2 32 16 22 0,014 0,014 41 0.1 0.1 3 1.8 1.2 23 0.2 0.3 42 0.7 0.8 4 0.2 0.1 24A 0.1 0.1 43 0.8 0.9 5 0.72 0.76 24B 0.1 0.1 44 0.01 0.01 6 13 12 25A 0.01 0.08 45 0.01 0.01 7 0.8 0.9 25B 0.09 0.09 46 0.01 0.01 8th 0.32 0.41 26 0.08 0.08 47 0.01 0.01 9 8.1 10 27 0.97 2.0 48 0.09 0.08 10 9.0 10 28 0.04 0.08 49 0.01 0.07 11 0.32 1.0 29 0.1 0.1 50 0.01 0.03 12 1 2 30 0.1 0.4 51 0.08 0.1 13A 0.1 0.2 31 0.08 0.1 52 0.01 0.07 13B nd nd 32 0.2 0.1 53 0.16 0.19 14 0.1 0.1 33 0.9 0.8 54 0.10 0.09 15 0.7 1.0 34 0.1 0.1 55 0.26 0.2 16 0.1 0.05 35 0.4 0.4 56 0.01 0.08 17 0.2 0.2 36 0.1 0.2 57 0.01 0.08 18 8th 5 37 0.1 0.4 58 0.09 0.01 19 3.3 4.3 38 0.2 0.3 59 0.7 1.2 20 2.3 7.0 39 0.1 0.1 Ref. 1 * 0.4 0.3 Table 1

• nd = not determined
• * Ref. 1 Table 1: The reference compound (reference substance) used in Example 10 of WO 1998/34947 (8S, 11R, 13S, 14S, 17S) -17-hydroxy-11- [4- (hydroxymethyl) -phenyl] -13-methyl-17-pentafluoroethyl-1,2,6,7,8,11, 12,13,14,15,16,17-dodecahydro-cyclopenta [a] phenanthrene-3-one.

Example 61

Determination of metabolic stability in human and rat liver microsomes

It were isolated human liver microsomes (HLM) for the evaluation of metabolic stability of compounds of the general Formula I used.

The Incubations were with 2.4 ml HLM solution (0.5 mg / ml protein content), 30 μl of the test compound (final concentration 1 μM) and 0.6 ml of the cofactor mixture (= NADPH-generating system 3 IU glucose-6-phosphate dehydrogenase, 14.6 mg glucose-6-phosphate, 1.2 mg NADP) at 37 ° C in 100 mM phosphate buffer at pH 7.4 carried out. There were 6 times (2-60 min) taken samples, precipitated with the same volume of methanol and the recovery of the test substances used in the supernatant determined by LC-MS / MS analysis. From the determined Half-life of the substance degradation was the so-called intrinsic Clearance of the substance calculated in the liver microsome approach. With help this became with the help of different physiological characteristics (human liver blood flow: 1.3 L · kg / h; specific liver weight (per kg of body weight): 21 g / kg; Microsomal protein content: 40 mg / g liver) according to the well-stirred model one (metabolic) predicts in vivo clearance in relation to phase I reactions.

Furthermore, assuming that (i) the absorbance of the test substance is 100%, and (ii) the first pass is completely mapped by the liver microsomal metabolism, a maximal oral biover availability (Fmax).

The tested compounds show surprisingly high metabolic stability (small on the basis of the in vitro data predicted "clearance" rate) and a good predicted maximum oral bioavailability F _max (Table 2).

• * Ref. 1 Tabelle 2: Als Vergleichsverbindung (Referenzsubstanz) dient die in Beispiel 10 der WO 1998/34947 beschriebene Verbindung (8S,11R,13S,14S,17S)-17-Hydroxy-11-[4-(hydroxymethyl)-phenyl]-13-methyl-17-pentafluorethyl-1,2,6,7,8,11,12,13,14,15,16,17-dodecahydro-cyclopenta[a]phenanthren-3-on.

In addition, some compounds have an unusually good solubility in aqueous medium under physiological conditions for this class of drugs (Table 2). Table 2: Ex. predicted clearance [l / h / kg] predicted F _max [%] (maximum oral bioavailability) Solubility at pH 7.4 [mg / l] humanely rat humanely rat Ref. 1 * 0.7 0.8 42 80 17 1 0.32 0.9 76 78 13 2 0.00 0.0 100 100 178 4 0.09 0.2 93 96 8th 5 0.17 0.9 87 78 8th 11 0.49 0.2 63 94 30 13A 0.31 0.0 77 100 148 16 0.33 0.0 75 100 204 17 0.08 0.0 94 100 204 24A 0.88 2.2 34 49 5 25A 0.70 0.9 47 79 5 31 1.13 0.9 15 78 10 34 1.21 1.4 9 68 7 36 0.60 0.5 55 88 4

• * Ref. 1 Table 2: The comparative compound (reference substance) used in Example 10 of WO 1998/34947 (8S, 11R, 13S, 14S, 17S) -17-hydroxy-11- [4- (hydroxymethyl) -phenyl] -13-methyl-17-pentafluoroethyl-1,2,6,7,8,11, 12,13,14,15,16,17-dodecahydro-cyclopenta [a] phenanthrene-3-one.

The Comparative compound has a good predicted maximum bioavailability in the rat, but not in humans.

Especially therefore preferred are those compounds which predicted one maximum oral bioavailability in different species (Rat, human), each larger 50% is.

All particularly preferred are those compounds which predicted one maximum oral bioavailability in different species (Rat, human), each larger 70% is. Examples include compounds of the examples 1, 2, 4, 5, 13A, 16 and 17.

Also particularly preferred are compounds having improved solubility. Examples include compounds of Examples 2, 11, 13A, 16 and 17.

Example 62

Determination of clearance and half-life after intravenous administration in rats

The determination of the in vivo clearance and half-life of test substances was carried out in female rats weighing about 200-250 g. For this purpose, the test substances (in the case of a cassette experiment up to 3 different substances per animal) in dissolved form at a dose of 0.3-0.5 mg / kg as bolus in the volume of 2 ml / kg administered intravenously (iv) in the tail vein, using compatible solubilizers such as PEG400 and / or ethanol in a tolerated amount. From a polyurethane catheter in the jugular vein were at the time points 2 minutes, 8 min, 15 min, 30 min, 45 min, 1 h, 2 h, 4 h, 6 h, 8 h, 24 h about 0.2 mL blood samples taken. The blood samples were stored without agitation in lithium-heparin tubes (Monovettes ^® from Sarstedt) and centrifuged for 15 min at 3000 rpm. An aliquot of 100 μL was taken from the supernatant (plasma) and precipitated by adding 400 μL of cold methanol. The precipitated samples were frozen overnight at -20 ° C, then again centrifuged at 3000 rpm for 15 min before removing 150 μL of the clear supernatant for concentration determination. The analysis was carried out by an Agilent 1200 HPLC system with connected LCMS / MS detection.

Calculation of PK parameters (via not linear regression by PK calculation software):

• CLplasma: total plasma clearance of the test substance (in L · kg / h), where CL plasma = dose / AUCinf;
• AUCinf: extrapolated area under the plasma concentration-time curve (in μg · h / L);
• CLblood: total blood clearance of the test substance (in L · kg / h), in which (CLblood = CLplasma * Cp / Cb);
• Cb / Cp: ratio of blood to plasma concentration distribution the test substance;
• T1 / 2: terminal half-life of the test substance (in H).

Table 3 example CL _blood [L / h / kg] t _1/2 [h] 1 0.9 ± 0.08 12.3 ± 0.3 4 3.3 ± 1.3 1.1 ± 0.7 16 2.1 ± 0.5 2.2 ± 0.4 17 0.7 ± 0.1 4.0 ± 0.8

Especially preferred are compounds having a terminal half-life of at least 1 hour in the rat. For example, called be compounds of Examples 1, 4, 16 and 17.

All particularly preferred are compounds having a terminal half-life of more than 8 hours and at the same time a blood clearance of less than 1.3 l / h / kg in the rat. For example, be mentioned the compound of Example 1.

Example 63

Abortive test on female rats

The Effect of progesterone and the progesterone receptor are for a successful pregnancy or pregnancy Mammals basic requirement. The progesterone antagonist Effect of the compounds of the invention was in pregnant rats (6 rats per group) on day 5 bis 7 post coitum under conventional housing and feeding conditions tested.

To successful mating, the pregnant animals (presence of sperm in the vaginal swab on day 1 of pregnancy = d1 p. c.) and divided into the treatment and control groups. The animals were then subcutaneously orally each 0.15; 0.5; 1.5 or 5 mg / kg of the test compound or 1.0 ml / kg of vehicle (benzyl benzoate / castor oil: 1 + 4 [v / v]) daily from day 5 to day 7 (d5-d7 p. c.).

The autopsy was performed on day 9 (d9 pc). As a measure of the progesterone receptor antagonistic effect of the uterus was examined for the presence of Nidationsstellen. The complete absence, but also the presence of pathological, haemorrhagic or otherwise abnormal sites of nidation on day 9 (d9 pc) was considered abortion. The results of the tests are shown in Table 4. Table 4: test compound Daily dose [mg / kg] po Abortion rate [%] vehicle 0 example 1 0.5 100 1.5 100 5.0 100 Example 16 0.5 0 1.5 16.7 5.0 100

QUOTES INCLUDE IN THE DESCRIPTION

This list The documents listed by the applicant have been automated generated and is solely for better information recorded by the reader. The list is not part of the German Patent or utility model application. The DPMA takes over no liability for any errors or omissions.

Cited patent literature

• - RU 486 [0002]
• - EP 057115 [0002]
• WO 98/134947 [0003]
• WO 98/34947 [0003, 0004]
• WO 2008/058767 [0004]
• WO 96/15794 [0036]
• WO 96/03130 [0036]
• - EP 2009/003249 [0036]
• WO 01/47490 [0067, 0067]
• WO 06/010097 [0067]
• WO 1998/34947 [0175, 0180]

Cited non-patent literature

• U. Fuhrmann et al., J. Med. Chem. 43, 5010-5016 (2000) [0003]
• - Remington's Pharmaceutical Science, 15th ed Mack Publishing Company, East Pennsylvania (1980) [0064]
• Tetrahedron Lett. 26, 2069-2072 (1985) [0082]

Claims (16)

17-Hydroxy-17-pentafluoroethyl-estra-4,9 (10) -diene-11-ethynylphenyl derivatives of the formula I

wherein R ^{1 is attached} via a C-C triple bond in position m or p to the phenyl ring and a radical is - (CH = CH) _n -R ² , - (CH ₂ ) _q -R ³ or -CH = NOR ⁴ , R ^{2 is} hydrogen or an aryl, C ₁ -C ₁₀ alkyl, -CO ₂ R ⁶ or -CN group, R ^{3 is} hydrogen, NH ₂ , N ₃ or an -NHCONHR ⁴ , -OCONHR ⁴ , -OR ⁵ group R ^{4 is} selected from the group comprising hydrogen, C ₁ -C ₁₀ alkyl, C ₂ -C ₁₀ alkenyl, aryl, C ₇ -C ₂₀ aralkyl, (CH ₂ ) _s -R ⁶ , CH ₂ -CO-OR ⁶ ,

wherein R ^{5 is} selected from the group comprising hydrogen, C ₇ -C ₂₀ aralkyl, CH ₂ CO ₂ R ⁶ , CH ₂ CN, CH ₂ CH ₂ OH,

n is 0 to 2, q is 1 or 2, s is 1 or 2, R ^{6 is} hydrogen, C ₁ -C ₁₀ alkyl, aryl, C ₇ -C ₂₀ aralkyl, X is oxygen, NOR ⁶ or an NNHSO ₂ R ⁶ group, with R ⁶ in the meaning indicated, and their salts, solvates or solvates of the salts, including all crystal modifications, the α-, β- or γ-Cyclodextrinclathrate, as well as the liposome-encapsulated compounds. Compounds according to claim 1 wherein X is Oxygen stands. Compounds according to claim 1 wherein the group

in para position to the phenyl ring is attached. Compounds according to any one of claims 1-3 present as solvate. Compounds according to Claim 1 or 2, in which R ^{1 represents} a - (CH =CH) _n -R ² or a - (CH ₂ ) _q -R ³ group, with n, q, R ² and R ³ in the meanings indicated, stands Compounds according to claim 1 or 2, wherein R ^{2 is} a group COOH and R ^{3 is} a group -OR ⁵ with R ⁵ meaning CH ₂ CO ₂ H or CH ₂ CH ₂ OH. Compounds according to any one of claims 1-4 wherein the group R ¹ terminally carries a carboxylic acid group or an alcohol group. Compounds according to claim 1 which are - (8S, 11R, 13S, 14S, 17S) -17-hydroxy-11- [4- (3-hydroxy-prop-1-yn-1-yl) -phenyl] -13-methyl -17-pentafluoroethyl-1,2,6,7,8,11,12,13,14,15,16,17-dodecahydrocyclopenta [a] phenanthren-3-one - (E) -5- [4 - (( 8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13,14,15,16,17 -dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -pent-2-en-4-in-nitrile - (Z) -5- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene -11-yl) -phenyl] -pent-2-en-4-in-nitrile - (8S, 11R, 13S, 14S, 17S) -17-hydroxy-11- {4- [3- (2-hydroxyethoxy) prop-1-yn-1-yl] phenyl} -13-methyl-17-pentafluoroethyl-1,2,6,7,8,11,12,13,14,15,16,17-dodecahydro-cyclopenta [a] phenanthrene-3-one - 3 - {(E) -4- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl] 2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -but-1-en-3- inyl} benzoic acid {3- [4 - ((8S, 11 R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro 1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyloxy} -acetonitrile - 4- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13- methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) phenylethynyl ] benzoic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12 , 13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) phenylethynyl] benzoic acid methyl ester - (8S, 11R, 13S, 14S, 17S) -11- (4-ethynyl) phenyl) -17-hydroxy-13-methyl-17-pentafluoroethyl-1,2,6,7,8,11,12,13,14,15,16,17-dodecahydro-cyclopenta [a] phenanthrene-3-one - (8S, 11R, 13S, 14S, 17S) -11- [4- (3-azido-prop-1-yn-1-yl) -phenyl] -17-hydroxy-13-methyl-17-pentafluoroethyl-1 , 2,6,7,8,11,12,13,14,15,16,17-dodecahydro-cyclopenta [a] phenanthrene-3-one - (E) - [4 - (8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodec ahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -propinal O-benzyl-oxime and (Z) - [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13 -methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) - phenyl] -propinal O-benzyl-oxime - (E) - [4 - ((8 S, 11 R, 13 S, 14 S, 17 S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3, 6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -propinal O-ethyl-oxime and (Z) - [ 4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13,14,15 , 16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -propinal O-ethyl-oxime - [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy 13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -propinal O-isobutyl-oxime - 1- (3,5-dimethyl-isoxazol-4-yl) -3- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17- hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthr en-11-yl) -phenyl] -prop-2-ynyl} urea - 1- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3- oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop 2-ynyl} -3-isopropylurea - 3- (3- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl -2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop-2-ynyl} - ureido) -propionic acid ethyl ester - 1-ethyl-3- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3, 6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl} -urea - 1- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12 , 13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl} -3- (4-methoxy-phenyl) -urea - 1- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13 , 14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl} -3-phenyl-urea - 1- {3- [4 - (( 8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13,14,15,16,17 -dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl} -3- (4-fluoro-phenyl) -urea - 1-benzyl-3- {3- [4- ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13,14,15,16 , 17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl} -urea - 1-allyl-3- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop-2-ynyl} -har Substance - allylcarbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11 , 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl ester - ethyl-carbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro 1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl ester) - phenyl-carbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy- 13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop-2-ynyl ester - 4-methylphenylcarbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl- 2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl ester - 4 Fluorophenyl carbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11, 12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthr en-11-yl) -phenyl] -prop-2-ynyl ester - isopropylcarbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo 17-pentafluoroethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop-2- inyl ester - benzylcarbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8, 11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl ester - (8S, 11R, 13S, 14S, 17S) -17-hydroxy-11- [4- (3-Methanesulfonyl-phenylethynyl) phenyl] -13-methyl-17-pentafluoroethyl-1,2,6,7,8,11,12,13,14,15,16 , 17-dodecahydro-cyclopenta [a] phenanthren-3-one - 4-methoxyphenylcarbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo 17-pentafluoroethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop-2- inyl ester - 4- {3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8, 11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop-2-yn-oxycarbonylamino} -benzoic acid ethyl ester - (4-piperidin-1-yl-phenyl) -carbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy-13- methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl ] -prop-2-ynyl ester - (8 S, 11 R, 13 S, 14 S, 17 S) -17-hydroxy-11- [4- (4-methanesulfonylphenylethynyl) -phenyl] -13-methyl-17-pentafluoroethyl-1 , 2,6,7,8,11,12,13,14,15,16,17-dodecahydro-cyclopenta [a] phenanthren-3-one - 3-pyridylcarbamic acid 3- [4 - ((8S, 11R , 13S, 14S, 17S) -17-hydroxy-13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro- 1H-cyclopenta [a] phenanthren-11-yl) -phenyl] -prop-2-ynyl ester - tert-butyl-carbamic acid 3- [4 - ((8S, 11R, 13S, 14S, 17S) -17-hydroxy- 13-methyl-3-oxo-17-pentafluoroethyl-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene-11-yl) -phenyl] -prop-2-ynyl ester Process for the preparation of the compounds of general formula I, characterized in that a phenylsulfonate of general formula II,

wherein R ^{1 'is} a perfluorinated C ₁ -C ₁₀ alkyl group, X' is an oxygen atom, two alkoxy groups OR ⁷ , a C ₂ -C ₁₀ alkylene-α, ω-dioxy group which may be straight-chain or branched, R ⁷ C ₁ C ₄ alkyl, R ^{8 is} hydrogen, R ^{9 is} a hydroxyl group, or R ⁸ , R ⁹ together represent a bond by palladium-catalyzed coupling reactions in a compound of general formula I '

wherein R ¹ , X ', R ⁸ and R ^{9 have} the abovementioned meanings, and optionally converts existing functionalities in R ¹ and / or further subsequent reactions to compounds of general formula I' and then from the group X 'is a group X. with X as oxygen releases and this carbonyl group (X = oxygen) optionally further functionalized and converted to a group with X in the meaning of NOR ⁶ or NNHSO ₂ R ⁶ and / or for the case R ^{8 is} hydrogen and R ^{9 represents} a hydroxyl group, generates a double bond by elimination of water and thus R ⁸ and R ^{9 represent} a common bond. Compounds according to any one of claims 1-8, the one progesterone receptor antagonistic effect in stable Show transfectants of human neuroblastoma cells. Compounds according to any one of claims 1-8, in vitro in stable transfectants of human neuroblastoma cells on the progesterone receptor an antagonistic potency with IC50 values of 1 nM or less. Compounds according to any one of claims 1-8, which predicted a different species (rat, human) have maximum oral bioavailability, respectively is greater than 50% and where the species-specific Differences in bioavailability not greater than 20% are. Compounds according to any one of claims 1-8, which predicted a different species (rat, human) have maximum oral bioavailability, respectively greater than 70% and where the species-specific Differences in bioavailability not greater than 15% are. Pharmaceutical preparations containing at least one compound according to any one of claims 1-8 or 10-13 or mixtures thereof and pharmaceutically acceptable carriers. Use of the compounds according to claim 1-8 or 10-13 for the manufacture of a medicament. Use of the compounds according to claim 1 for the manufacture of a medicament for the treatment and / or prophylaxis of uterine fibroids (myomas, uterine lineaments), endometriosis, severe menstrual bleeding, meningiomas, hormone-dependent Breast cancers and menopausal symptoms or for fertility control and emergency contraception.